Hi everyone!

My name is Katie Pickup and I wanted to introduce myself as I’m a new Reviews Editor at The Company of Biologists. I am going to be working with Development and the Node, as well as with three of the Company’s other journals (Journal of Cell Science, Disease Models & Mechanisms and Journal of Experimental Biology). I’m really looking forward to being exposed to a broad range of bioscience topics in this role.

My research background is mainly in stem cell biology. I did my PhD at the MRC Human Genetics Unit at the University of Edinburgh investigating the role of DNA methylation in pluripotency and differentiation of mouse embryonic stem cells in Richard Meehan’s lab. I used 3D models of differentiation including gastruloids and embryoid bodies to understand the impact of DNA hypomethylation on cell lineage trajectories and exit from pluripotency. I’m particularly interested to see where stem cell-based embryo model research goes over the next few years, both scientifically and from the regulatory side. I’m also excited for the opportunity to branch out in my new role as an editor and learn more about other areas of developmental biology across the spectrum of model organisms.

I’m really looking forward to getting to know the wider community better through working with authors on Review articles and other front-section journal content like interviews and poster articles. I also can’t wait to travel to lots of different conferences and workshops across the world, so hopefully I’ll get to meet some of you there! In the meantime, feel free to get in touch via email, LinkedIn or X. 

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When I joined the Zon lab in June 2021, my mentor, Leonard Zon, shared an insightful piece of advice: “A good project always has two questions, one you can answer and one you dream of answering.” In this post, I’ll focus on that dream.

In brief, the question we managed to answer – at least a little bit – is how to instruct the expression of  the “eat-me” signal driven by Calreticulin (CALR) and its complementary “don’t-eat-me” signal, driven  by beta-2-microglobulin (B2M). In our study (https://www.science.org/doi/10.1126/science.adn1629) , we showed that high levels of reactive oxygen species (ROS) leads to high surface presentation of Calr, which, in turn, leads to high levels of interaction with a macrophage, and clearance of the stressed hematopoietic stem and progenitor cell (HSPC). On the flip side, TLR3 can modulate the expression of CALR together with B2M. Here, the balance between these molecules leads to a scenario where a macrophage interacts with the HSPCs, but does not “eat” them. This intricate signaling impacts clonal diversity, revealing a potential avenue for future immunotherapies targeting mutant or cancerous stem-cell populations while sparing healthy ones.

Our uncharted territory lies in harnessing macrophages to selectively target malignant clones. We found higher B2M expression in HSPCs from acute myeloid leukemia (AML) patients with malignant stratification, suggesting that malignant clones may exploit B2M to evade macrophage clearance. This paves the way for drug development aimed at eliminating pre-leukemic and leukemic cells via macrophage-mediated clearance. This idea may also be further explored in aging studies, in which one could teach the macrophage to eliminate aged progenitor cells.

Another aspect of our study that could be further explored relies on a key finding that repetitive elements (RE), including Ltr, are the endogenous ligand of the Tlr3 and triggers b2m expression via the tlr3/irf3 pathway. We observed that these endogenous REs promoted high levels of ISG15, a gene linked to the type I interferon response.

Given the evolutionary conservation of RE and B2M, we explored the significance of this mechanism in both fish and humans, focusing on pathogen infections that are a common threat to both species. Specifically, we examined the role of TLR3 signaling in inducing “emergency granulopoiesis,” a protective process that accelerates neutrophil production during severe infection. Upon poly I:C stimulation, neutrophil populations increased.

Although further studies are needed to strengthen the relevance of this phenomenon, our results suggest that viral stimulation may confer a better fit against opportunistic pathogens by promoting granulocyte differentiation. This observation gets more fascinating if one considers that this increase of type I response could not only alter the emergency granulopoiesis, but also contribute to innate immune training. Seminal studies have shown that type I IFN signaling mediates neutrophil trained innate immunity, mainly in the context of solid cancer. This therefore suggests that RE-triggered type I interferon may play a role in trained immunity—a concept previously explored in cancer but now potentially relevant in other systems.

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Over the summer, I had the opportunity to conduct research in Vivian Li’s Lab, focusing on the role of WNT signalling in the response of intestinal stem cells to injury, under the expert guidance of Dr. James Wilmouth Jr. As a medical student, I am deeply appreciative of the opportunity to gain hands-on experience in fundamental research through undertaking a project over the course of two months. I am truly inspired by the continuous innovation at the Francis Crick Institute, driven by a diverse community of committed scientists who embrace collaboration and interdisciplinary approaches.

One research axis within the Li Lab focuses on how canonical WNT signalling maintains intestinal stem cells (ISCs) and influences cell fate decision. The gut epithelium can be organised into an architecture of crypts and villi (Fig 1A). Crypts are found at the base, extending into the villi towards the gut lumen. ISCs are located within the crypt and responsible for driving renewal of the gut epithelium every 3-5 days during homeostasis. High WNT signalling in the crypts maintains ISC homeostasis before decreasing along a gradient towards the villi. Publications have demonstrated that whilst inhibiting WNT signals causes degeneration, WNT overactivation induces adenoma formation. Therefore, fine-tuned WNT signalling is crucial for maintaining ISC homeostasis.

For this project, I examined the role of WNT signalling in ISCs during injury-induced regeneration. We utilized whole-body irradiation to simulate ISC injury-induced regeneration in mice. This model results in crypt degeneration at 1-day post-irradiation (dpi), followed by regeneration at 3 dpi, and recovery by 7 dpi (Fig 1B). Intestinal tissues were harvested for crypt isolation at four time points: 0 dpi (pre-irradiation control), 1 dpi, 3 dpi, and 7 dpi. These samples were then used to investigate three transcriptional signatures throughout the regenerative process: Classical Intestinal Stem Cell (ISC), Revival Stem Cell (RevSC), and WNT target genes.

I performed quantitative PCR (qPCR) to analyse the temporal changes in gene expression during the regenerative process (Fig 2). Results indicated that classic ISC markers were downregulated at 1 dpi following injury and recovered to near homeostatic levels by 7 dpi. RevSC markers showed an induction at 1 dpi, followed by a decline toward baseline levels by 7 dpi. Interestingly, WNT target gene expression remained relatively stable throughout the 7-day period.

These initial results suggest that both Yap-driven RevSC signature and certain WNT targets are expressed during injury-induced regeneration. This contradicts the current understanding, which proposed an antagonistic relationship between YAP and WNT during ISC regeneration up on injury. To further investigate the co-expression of RevSC markers and WNT in ISCs, we utilised immunohistochemistry (IHC) and flow cytometry of WNT reporter mice in the irradiation induced regeneration model (Fig 3).

To spatially characterise WNT-high cells in the crypts co-expressing the Revival Stem Cell (RevSC) signature, I conducted IHC using a TCF/Lef:H2B;mCherry reporter system. The reporter has Tcf/Lef binding sites which drive the expression of the H2B:mCherry fluorescent protein, enabling visualisation of active WNT signalling. I observed colocalisation of mCherry and Clu (RevSC marker) at 1dpi, which was more pronounced at 3dpi (Fig 3A). These results suggest that WNT-high ISCs express RevSC markers during regeneration. In order to quantify how often this happens during regeneration, I utilised flow cytometry. By gating for mCherry+ ISCs (WNT-high ISCs), I found there was a significant increase in the percentage of mCherry+ ISCs expressing the RevSC marker Sca1 at 3dpi (~20%) compared to 0 dpi (~3%) (Fig3B).

In conclusion, my project demonstrated that a proportion of WNT-high ISCs co-express RevSC markers during injury-induced regeneration. Although preliminary, these results highlight that it is necessary to further investigate the role of YAP in the interplay between WNT signalling and the RevSC signature in ISCs during regeneration. This work would provide clarity into which signals dictate ISC survival during regeneration.

This project has provided me with invaluable insight into the scientific process. I have learned advanced techniques at the Li lab, including organoid culture and maintenance. I would like to thank my supervisor, James, for his exceptional mentorship in building my critical thinking, guiding my experiments, and supporting my data analysis and interpretation. I would also like to extend my thanks to the Francis Crick Institute and the Medical Research Foundation Rosa Beddington Fund for their generous support, which has enabled me to contribute to this exciting field of research.

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Brown algae are a group of complex multicellular eukaryotes, unrelated to animals, plants and fungi. It follows that brown algae evolved the process of multicellular development independently, offering a unique opportunity to investigate shared principles underlying developmental evolution across the tree of life. One such principle is the hourglass model of embryo evolution. The hourglass model describes a pattern of evolutionary conservation and divergence during embryogenesis, where the divergent earlier and later stages are bridged by a conserved mid-embryonic period (Duboule 1994). Such hourglass patterns have been observed in animal, plant and fungal development (Drost et al. 2017). But what about brown algae?

In our recent paper, “A transcriptomic hourglass in brown algae” (Lotharukpong et al. 2024), we asked a simple question: does brown algal development follow the hourglass model? By profiling the developmental transcriptome in two Fucus species, we observe an hourglass pattern in brown algal embryogenesis (Fig 1). The conserved mid-embryonic period is underpinned by the reduced expression of evolutionarily younger genes and the presence of more broadly expressed, potentially pleiotropic genes. We also explored the transcriptome across life cycle stages in brown algae with differing levels of morphological complexity. Crucially, in morphologically simple Ectocarpus species without canonical embryos, multicellular development itself appeared to constrain transcriptome evolution, suggesting how such embryo hourglass patterns may have emerged in the first place (at least in brown algae). Overall, this work gives evidence for the hourglass model as a general principle underlying developmental evolution across the tree of life.

But as we all know; a lot went on behind the paper.

Sampling and growing brown algal species:

To test the hourglass model in brown algae, we first had to literally find morphologically complex brown algae that undergo embryogenesis (Fig 2). Between France and Germany, Rémy Luthringer (co-author) had to go collect reproductively mature adults to produce embryos and cultivate them in the lab. It was a challenge to culture Fucus embryos beyond the earliest embryonic stages, since they require a lot of care to ensure healthy growth. This was all the more difficult for species such as F. distichus, which required up to half a year to reach the latest embryonic stage used in the study.

Bioinformatics in the spotlight:

We then faced several hurdles on the bioinformatics side when piecing this study together, which required a sustained push on software development. In particular, we wanted to infer the evolutionary age of each gene, which is needed for computing the transcriptome age index (a key metric for evolutionary transcriptomics). Existing approaches were not suitable nor computationally scalable to current large databases such as the National Center for Biotechnology Information (NCBI) non-redundant (nr) database and did not account for potential database contaminations among other confounding factors in gene age inference. We therefore teamed up with Josué Barrera-Redondo to create GenEra (Barrera-Redondo et al. 2023), a wrapper around the fast and sensitive pairwise sequence aligner DIAMOND v2 (Buchfink et al. 2021), which brought down the search time from months to days. This finally allowed us to infer the gene age in a timely manner for any eukaryotic genome, including the species we used in the hourglass study (Fucus serratus, Fucus distichus, Ectocarpus sp., Laminaria digitata and Saccorhiza polyschides).

On top of this, we extended the functionalities of R packages for evolutionary transcriptomics, such as myTAI (Drost et al. 2018), to accommodate our analyses. New and existing functions in myTAI enabled us to distinguish evolutionary signals from random noise. We hope these efforts will be useful for the wider community interested in asking evo-devo questions using transcriptomic data.

What’s next for the story?

It is an exciting time for brown algal research. A recent study has provided several dozen genome assemblies across major groups of brown algae (Denoeud et al. 2024). Furthermore, functional genetics is now a possibility for multiple brown algal species, fuelling recent findings such the independent evolution of HMG domain genes as a male sex-determining factor (Luthringer et al. 2024). There is also a drive to generate transcriptomic data to understand cell-type and tissue evolution in brown algae, which also evolved cell-types and tissues independently from other complex multicellular eukaryotes. There is still much more to come!

References

Barrera-Redondo J, Lotharukpong JS, Drost H-G, Coelho SM. 2023. Uncovering gene-family founder events during major evolutionary transitions in animals, plants and fungi using GenEra. Genome Biol. 24:54.

Buchfink B, Reuter K, Drost H-G. 2021. Sensitive protein alignments at tree-of-life scale using DIAMOND. Nat. Methods 18:366–368.

Denoeud F, Godfroy O, Cruaud C, Heesch S, Nehr Z, Tadrent N, Couloux A, Brillet-Guéguen L, Delage L, Mckeown D, et al. 2024. Evolutionary genomics of the emergence of brown algae as key components of coastal ecosystems. :2024.02.19.579948. Available from: https://www.biorxiv.org/content/10.1101/2024.02.19.579948v2

Drost H-G, Gabel A, Liu J, Quint M, Grosse I. 2018. myTAI: evolutionary transcriptomics with R. Bioinformatics 34:1589–1590.

Drost H-G, Janitza P, Grosse I, Quint M. 2017. Cross-kingdom comparison of the developmental hourglass. Curr. Opin. Genet. Dev. 45:69–75.

Duboule D. 1994. Temporal colinearity and the phylotypic progression: a basis for the stability of a vertebrate Bauplan and the evolution of morphologies through heterochrony. Development 1994:135–142.

Lotharukpong JS, Zheng M, Luthringer R, Liesner D, Drost H-G, Coelho SM. 2024. A transcriptomic hourglass in brown algae. Nature 635:129–135.

Luthringer R, Raphalen M, Guerra C, Colin S, Martinho C, Zheng M, Hoshino M, Badis Y, Lipinska AP, Haas FB, et al. 2024. Repeated co-option of HMG-box genes for sex determination in brown algae and animals. Science 383:eadk5466.

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It’s now been 13 months since I started my lab, marking the end of my ‘New PI Diaries’ series here on the Node. The journey has so far been both overwhelming and rewarding, and I’ve enjoyed the chance to reflect and share my experiences in this blog. Overall, it’s been a lot—but mostly a good lot. My time gets split between a lot more responsibilities and I have less time to be in the lab. Both mentoring and teaching now take up much more time than during my postdoc, but luckily, I already know I enjoy both.

However, one aspect that was almost completely new to me was managing lab finances. In this blog, I want to share some examples of situations I encountered and the lessons I learned, along with a few key takeaways. To provide some context, my Independent Junior Group Leader position comes with support that includes a PhD student position, a technician, a yearly consumables budget, and some startup funds. Comparing lab resources across universities and countries is difficult. For instance, my startup budget is considerably smaller than those typically offered at US universities but potentially bigger than that available at other institutes or universities. However, I also benefit from funded positions and an equipped lab. In addition, many larger pieces of equipment and facilities are shared within the institute and can be used free of charge or at a low rate, reducing my need to purchase new equipment.

But let’s talk people first. In addition to support from the ZMBP, I was able to secure an Emmy Noether grant from the DFG. This grant covers my salary for six years, along with funding four years of two PhD students and a postdoc, allowing for steady growth and stability in the coming years. However, I quickly ran into an unexpected issue: the PhD student position from the University is paid a lower salary compared to the positions provided by the DFG. Different enough to feel unfair but unfortunately it is common. Similarly, PhD positions in different disciplines get compensated at different rates. Now, I cannot change decisions of the University or the state of Baden-Württemberg, but I figured there must be a workaround.  Once I started asking around, I learned that people have come up with a variety of solutions. Talking with fellow group leaders and our Head of Central Services I learned that we could reassign the unused % of the technician position together with some flexible lab budget to equalize the PhD salaries. So, it’s important not to hesitate in discussing challenges; I certainly wasn’t the first to face this problem, and people had already identified potential solutions.

Apart from people, we’re spending money on consumables and equipment. The ZMBP account, which includes a startup and a yearly budget, allows me flexibility in spending. Additionally, last year I received one time support from a collaborative project. This account had its own constraints, while flexible, the funds must be used within two months, adding some pressure. Finally, the Emmy Noether provides consumables funding, albeit with more limited flexibility since it is there to support the group and project and any equipment should be provided by the University. As a result, I got a crash course into which account to use for what purchase. In short: for me it’s best to save the ZMBP account for computer and equipment purchases as those cannot be made from all other accounts.

Most of the necessary equipment was actually already there, but I found several items that could significantly make our lab’s work easier and more efficient. Before purchasing these I first spent some time looking around, checking what is available already, what our need really is, and what options we have for financing the things we need.  And although I still don’t have a precise overview of our total finances, we’re in a fortunate position where I don’t have to stress excessively about money. I do feel it’s important for everyone in the lab to know the price of some of our reagents and equipment. Investing in reagents, such as 2x mixes for genotyping and colony PCR, is worth the costs right now for the time they save as long as people are aware of their cost. We’re in a good position, but I want to avoid wasting funds that could be better spent elsewhere to make our days easier. Eventually using lab funds we purchased two new stereomicroscopes to dissect Arabidopsis embryos, additional pipettes, and computers. Each piece of equipment or expensive kit is an investment that I think will pay off and that we can afford in our current situation. However, I remain careful as, well, I lack experience, and you never know what’s up ahead.

Here are my early-stage financial takeaways:

• People are expensive. Value the positions you have and hire carefully. In addition, sometimes spending more on consumables and equipment is worth the time saved for your team.
• Keep track of your accounts. Understand what’s in each account, what you can spend it on, and where your money is going. Is it what you expected?
• Use your funds. Once you have a clear overview, consider what tools could make lab operations smoother. I initially waited to determine which investments would be beneficial for everyone in the lab but then decided to make some investments.

And my personal goals:

• Have a more complete overview of the lab finances. I have a rough idea of what we’re spending and what’s available but I still have a long way to go. Luckily I have plenty of people to ask for advice.
• Get experience. While enthusiasm is important, it doesn’t replace experience. I’m learning a lot and I already feel a lot more confident in making these decisions.

While the lab’s immediate future is secure, I also need to plan for what comes next. To be honest, at this point, anytime I feel like I’m in control of things I realize I just have been forgetting or ignoring something important. I guess that’s life. In general, I think I should spend more time thinking of grants. Next year will be my final opportunity to apply for the ERC Starting Grant, so my focus will be on that. Additionally, in a few years, I’ll need to start searching for a professor position, as my ZMBP Junior Group Leader position and Emmy Noether funding will end in about five years, and securing a professorship in Germany can take some time.

Wish me luck!

First investment: new stereomicroscope for doing embryo dissection and the beautiful images it takes of GUS-stained seedlings.

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[Editorial from Development’s latest Special Issue ‘Uncovering Developmental Diversity’, edited by Cassandra Extavour, Liam Dolan and Karen Sears.]

Scanning through early issues of the Journal of Embryology and Experimental Biology (the previous name for this journal) reveals the diverse range of organisms that were investigated by developmental biologists in the 1950s and 1960s. However, the rise of molecular genetics in subsequent decades led to a narrowing in species choice to a small repertoire of well-characterised model organisms for which there were genetic tools for functional experimentation. In recent years, however, technological advances, including genome and transcriptome sequencing, flexible genome-editing approaches and high-resolution four-dimensional imaging, provide an opportunity to once again study developmental questions in organisms across all kingdoms of life. Given the current global challenges of climate change and biodiversity loss, it is particularly important that we turn our attention to understanding development in an unstable world.

This important topic was the basis of Development’s Journal Meeting, ‘Unconventional and Emerging Experimental Organisms in Cell and Developmental Biology’ in 2023, which you can learn more about in the Meeting Review published here (Lemke et al., 2024). Fuelled by the success of the meeting, we chose to focus this Special Issue, led by Academic Editor Cassandra Extavour, together with Liam Dolan and Karen Sears as Guest Editors, on a related topic: Uncovering Developmental Diversity. We are particularly delighted that multiple attendees from our meeting have contributed both research and review-type articles to this issue.

The 28 research papers in this Special Issue highlight 32 different organisms from across the multicellular tree of life, featuring cnidarians (Garschall et al., 2024), insects (Matsuda et al., 2024; Bai et al., 2024; Beaven et al., 2024; Pallarès-Albanell et al., 2024) and annelids (Bideau et al., 2024), as well as echinoderms (Barone et al., 2024; McDonald et al., 2024; Jackson et al., 2024; Clarke et al., 2024) and chordates (Gigante et al., 2024; Johnson et al., 2024), including vertebrates (Rees et al., 2024; Pérez-Gómez et al., 2024), many of which are various fishes (Leclercq et al., 2024; Li et al., 2024; Woronowicz et al., 2024; Peloggia et al., 2024; Jin et al., 2024). These articles demonstrate the importance of finding the best model to address a developmental question, such as making use of the curved epithelium in the sea star embryo to investigate cell organisation and packing (Barone et al., 2024) or using the regenerative capacity of annelids to learn more about cell plasticity (Bideau et al., 2024). In addition to annelids, a Perspective in this issue highlights five more ‘extraordinary’ model systems for regeneration across scales from single cells to whole organisms (Accorsi et al., 2024).

Not limited to animals, the Special Issue also embraces a wide array of studies uncovering fundamental developmental processes, such as axis formation and organogenesis in photosynthetic organisms, including brown algae (Vigneau et al., 2024; Boscq et al., 2024), liverworts (Attrill and Dolan, 2024; Attrill et al., 2024; Sakai et al., 2024), and vascular plants such as ferns (Woudenberg et al., 2024) and angiosperms (Mody et al., 2024; Spiegelhalder et al., 2024). Photosynthetic organisms feature heavily in the issue’s review-type content, too, with articles describing how brown algae can inform us about the transition to multicellularity (Batista et al., 2024), how the environment and climate change influence development through the lens of stomata (Chua and Lau, 2024) and what we can learn about the evolution of plant development through the fossil record (Hetherington, 2024).

The evo-devo field, in particular, has benefitted from the appreciation of biodiversity and increased taxonomic sampling. Reflecting this, two Reviews discuss fundamental evolutionary concepts, including how phenotypes can be maintained by different underlying genetic architecture through developmental systems drift (McColgan and DiFrisco, 2024), as well as a cautionary tale of how reports on the low-hanging fruit of simple genetic explanations of evolution should not change our perception that evolution is inherently complex (Cooper, 2024).

A broad selection of available organisms also allows the study of rare evolutionary innovations, such as the ability of Nematostella to degrow in response to food availability (Garschall et al., 2024) or of teleost fish to adapt ionocyte differentiation to regulate osmotic levels within aquatic environments (Peloggia et al., 2024). Adaptive plasticity is also the focus of a Review article describing how organisms assess environmental cues across scales and respond via phenotypic changes (Hill et al., 2024). Furthermore, capturing developmental biodiversity furthers our understanding of complex life cycles (McDonald et al., 2024; Peloggia et al., 2024) – a topic motivating a Hypothesis for unravelling cellular rejuvenation (Berger, 2024). Indeed, studying organisms with metamorphic life cycles allows us to learn about the intrinsic developmental process, such as how the rhinoceros beetle remodels its horn (Matsuda et al., 2024) or neuronal cell survival in Ciona (Gigante et al., 2024).

Importantly, research using emerging model systems relies on new tools that facilitate functional experiments. Our Techniques and Resources section features methods for the delivery of proteins and nucleic acids into oocytes in a variety of species (Clarke et al., 2024), as well as approaches for generating stable genetic lines (Jackson et al., 2024) and tools for quantifying diversity (Mody et al., 2024). However, not all species are amenable to being cultured in the lab, and a Perspective describes the importance of fieldwork for developmental biology in unconventional model systems (Brown et al., 2024). In addition, a Spotlight article describes how modern innovations in stem cell technology might be employed for species conservation (Hutchinson et al., 2024), highlighting how understanding biodiversity is the first step to its preservation, an increasingly prevalent topic in the context of climate change.

Overall, we hope that this issue demonstrates both how technological advances have made it possible to understand development and regeneration in previously intractable organisms, as well as the importance of this pursuit. We continue to ensure Development is an appropriate home for your studies in developmental biology, stem cells and regeneration using any organism. We welcome your submissions.

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Welcome to our monthly trawl for developmental and stem cell biology (and related) preprints.

The preprints this month are hosted on bioRxiv and arXiv – use these links below to get to the section you want:

Developmental biology

• Patterning & signalling
• Morphogenesis & mechanics
• Genes & genomes
• Stem cells, regeneration & disease modelling
• Plant development
• Environment, evolution and development

Cell Biology

Modelling

Tools & Resources

Research practice and education

Developmental biology

| Patterning & signalling

Hypomorphic NOTCH1 Expression Alters Cardiomyocyte Cellular Architecture in Hypoplastic Left Heart Syndrome

Jordann Lewis,  Travis B. Lear, Brent Schlegel, Dominic Woods, Krithika Rao, Amy Sentis,  Jay Tan, Rajaganapathi Jagannathan, Zaineb Javed, Aine N. Boudreau,  Timothy Nelson,  Mousumi Moulik,  Nadine Hempel, Bill B. Chen,  Sruti Shiva,  Dhivyaa Rajasundaram, Toren Finkel,  Anita Saraf

Collaborative role of two distinct cilium-specific cytoskeletal systems in driving Hedgehog-responsive transcription factor trafficking

Pei-I Ku,  Jamuna S Sreeja, Abhishek Chadha, David S Williams, Martin F Engelke, Radhika Subramanian

The C. elegans LON-1 protein requires its CAP domain for function in regulating body size and BMP signaling

Maria Victoria Serrano, Stephanie Cottier, Lianzijun Wang, Sergio Moreira-Antepara, Anthony Nzessi, Zhiyu Liu, Byron Williams, Myeongwoo Lee,  Roger Schneiter,  Jun Liu

An evolutionarily conserved role for VEGF signaling in the expansion of non-vascular tissue during regeneration

 Aaron M. Savage, Alexandra C. Wagner,  Ryan T. Kim, Paul Gilbert,  Hani D. Singer,  Erica Chen,  Elane M. Kim,  Noah Lopez,  Kelly E. Dooling,  Julia C. Paoli,  S.Y. Celeste Wu,  Sebastian Bohm,  Rachna Chilambi,  Tim Froitzheim,  Steven J. Blair,  Connor Powell,  Adnan Abouelela, Anna G. Luong,  Kara N. Thornton,  Benjamin Tajer,  Duygu Payzin-Dogru,  Jessica L. Whited

A spatially-resolved blueprint of the developing human lung reveals a WNT-driven niche for basal stem cells

Peggy P. Hsu,  Ansley S. Conchola,  Tristan Frum, Xiangning Dong, Lila Tudrick, Varun Ponnusamy, Michael S. Downey, Manqi Wu, Mengkun Yang, Yusoo Lee, Emma Niestroy, Yu-Hwai Tsai, Angeline Wu, Sha Huang, Ian A. Glass, Sofia D. Merajver,  Jason R. Spence

EPHA2 Regulates SOX2 during Esophageal Development

 Tianxia Li,  Yosuke Mitani,  Ricardo Cruz-Acuña, Tatiana A. Karaksheva,  Varun Sahu, Cecilia Martin,  Hiroshi Nakagawa,  Joel Gabre

BMP signaling modulations control primitive streak patterning

 Gaël Simon, Jean-Louis Plouhinec,  Pascale Gilardi-Hebenstreit,  Benoit Sorre,  Jérôme Collignon

doi: https://doi.org/10.1101/2024.10.01.616050

Single-nucleus transcriptomics of wing sexual dimorphism and scale cell specialization in sulphur butterflies

 Ling S. Loh,  Joseph J. Hanly,  Alexander Carter,  Martik Chatterjee, Martina Tsimba,  Donya N. Shodja,  Luca Livraghi,  Christopher R. Day,  Robert D. Reed,  W. Owen McMillan,  Gregory A. Wray,  Arnaud Martin

WNT-mediating TCF/LEF transcription factor gene expression in early human pluripotency and cell lineages differs from the rodent paradigm

Connor Ross,  Takuya Azami, Marika Salonna, Richard Gyuris,  Jennifer Nichols,  Stefan Hoppler

Cellular signalling protrusions enable dynamic distant contacts in spinal cord neurogenesis

 Joshua Hawley,  Robert Lea,  Veronica Biga,  Nancy Papalopulu,  Cerys Manning

MMP21 behaves as a fluid flow transported morphogen to impart laterality during development

Tim Ott, Amelie Brugger, Emmanuelle Szenker-Ravi, Yvonne Kurrle, Olivia Aberle, Matthias Tisler, Martin Blum, Sandra Whalen, Patrice Bouvagnet, Bruno Reversade, Axel Schweickert

Independent control of neurogenesis and dorsoventral patterning by NKX2-2

Sumin Jang, Elena Abarinov, Julie Dobkin, Hynek Wichterle

CMTM4 is an adhesion modulator that regulates skeletal patterning and primary mesenchyme cell migration in sea urchin embryos

Abigail E. Descoteaux, Marko Radulovic, Dona Alburi,  Cynthia A. Bradham

Evidence for strong cell-scale signalling during planar polarisation in the Drosophila wing

Alexandre Carayon,  David Strutt

Shh signaling directs dorsal ventral patterning in the regenerating X. tropicalis spinal cord

 Avery Angell Swearer, Samuel Perkowski,  Andrea Wills

Cluster Assembly Dynamics Drive Fidelity of Planar Cell Polarity Polarization

 Silas Boye Nissen,  Alexis T. Weiner, Kaye Suyama,  Pablo Sanchez Bosch, Song Song, Yuan Gu,  Alexander R. Dunn,  Jeffrey D. Axelrod

Capicua maintains anterior-posterior axis in Blattella germanica ovaries

 Nashwa Elshaer,  Jorge Escudero,  Maria-Dolors Piulachs

Shc1 cooperates with Frs2 and Shp2 to recruit Grb2 in FGF-induced lens development

Qian Wang, Hongge Li, Yingyu Mao, Ankur Garg, Eun Sil Park, Yihua Wu, Alyssa Chow, John Peregrin,  Xin Zhang

Characterization of Hippo Signaling Components in the Early Dorsal Pancreatic Bud

 Neha Ahuja,  Caitlin Maynard, Tyler Bierschenck,  Ondine Cleaver

Irx3/5 define the cochlear sensory domain and regulate vestibular and cochlear sensory patterning in the mammalian inner ear

Yuchen Liu,  Tianli Qin,  Xin Weng, Bernice Leung, Karl Kam Hei So, Boshi Wang, Wanying Feng, Alexander Marsolais, Sheena Josselyn,  Pingbo Huang, Bernd Fritzsch, Chi-Chung Hui,  Mai Har Sham

Differential Sensitivity of Midline Patterning to Mitosis during and after Primitive Streak Extension

 Zhiling Zhao,  Rieko Asai,  Takashi Mikawa

Notch, β-catenin and MAPK signaling segregate endoderm and mesoderm in the diploblast Nematostella vectensis

Emmanuel Haillot, Tatiana Lebedeva, Julia Steger,  Grigory Genikhovich, Juan D. Montenegro,  Alison G. Cole,  Ulrich Technau

| Morphogenesis & mechanics

Morphomechanic tuning of ERK by actin-TFII-IΔ regulates cell identity

 Qiao Wu,  Jian Zhang, Bing Long, Xiao Hu, Bruna Mafra de Faria, Stephen Maxwell Scalf, Kutay Karatepe, Wenxiang Cao, Nikolaos Tsopoulidis, Andres Binkercosen, Masaki Yagi, Aaron Weiner, Mary Kaileh, Enrique M. De La Cruz,  Ananda L Roy,  Konrad Hochedlinger,  Shangqin Guo

Anisotropic stretch biases the self-organization of actin fibers in multicellular Hydra aggregates

 Anaïs Bailles, Giulia Serafini, Heino Andreas,  Christoph Zechner,  Carl Modes,  Pavel Tomancak

Melanocyte differentiation and mechanosensation are differentially modulated by distinct extracellular matrix proteins

 Carole Luthold,  Marie Didion,  Emilio Benedum,  Ann-Kathrin Burkhart,  Nina Demmerle,  Gubesh Gunaratnam,  Vanessa Samira Rácz,  Markus Bischoff,  Annika Ridzal,  Sandra Iden

Rho/Rok-dependent regulation of actomyosin contractility at tricellular junctions controls epithelial permeability in Drosophila

 Thea Jacobs,  Jone Isasti Sanchez, Steven Reger,  Stefan Luschnig

Three-dimensional quantitative micro-elastography reveals alterations in spatial elasticity patterns of follicles and corpora lutea in murine ovaries during ageing

Anna Jaeschke, Matt S. Hepburn, Alireza Mowla, Brendan F. Kennedy,  Chii Jou Chan

Mechanical properties are tuned during development with the fibrous network nature of the Arabidopsis cell wall

Si Chen, Isabella Burda, Purvil Jani, Bex Pendrak, Meredith N. Silberstein, Adrienne H.K. Roeder

Mechanical control of germ cell specification in Arabidopsis anthers

Chan Liu, Hui Shi, Yuting Han, Pan Wang, Kexin Li, Zhishuai Zhang, Jiazheng Liu, Yafeng Zheng, Linlin Li, Limei Lin, Chen Liang, Binjun Qin, Hua Han, Shunong Bai, Xiao Liu, Wenqian Chen, Feng Zhao

Spatiotemporal dynamics of primary and motile cilia throughout lung development

 Stephen Spurgin, Ange Michelle Nguimtsop,  Fatima N. Chaudhry,  Sylvia N. Michki,  Jocelynda Salvador,  M. Luisa Iruela-Arispe,  Jarod A. Zepp,  Saikat Mukhopadhyay,  Ondine Cleaver

IGF2 mediates Hippo signaling to control liver size

 Zhenxing Zhong, Ruxin Jin, Yiting Zhong, Li Zhang, Deqian Chen, Zhihan Jiao, Fanhui Zhou, Rui Zhu, Jian Wu, Rui Dong, Kuiran Dong, Fei Lan, Yu Wang, Kun-Liang Guan,  Fa-Xing Yu

Mechanical regulation of tissue flatness in Marchantia

 Jordan Ferria, Carla J.A. Fournié, Magdalena H. Jankowska, Doron Grossman,  Adrienne H.K. Roeder,  Stéphanie Drevensek,  Arezki Boudaoud

A mitochondrial redox switch licenses the onset of morphogenesis in animals

Updip Kahlon, Francesco Dalla Ricca, Saraswathi J. Pillai,  Marine Olivetta,  Kevin M. Tharp,  Li-En Jao,  Omaya Dudin, Kent McDonald,  Mustafa G. Aydogan

Mechanochemical Patterning Localizes the Organizer of a Luminal Epithelium

Sera Lotte Weevers, Alistair D. Falconer, Moritz Mercker, Hajar Sadeghi, Jaroslav Ferenc, Albrecht Ott, Dietmar B. Oelz, Anna Marciniak-Czochra, Charisios D. Tsiairis

Tissue-Like Multicellular Development Triggered by Mechanical Compression in Archaea

Theopi Rados, Olivia S. Leland, Pedro Escudeiro, John Mallon, Katherine Andre, Ido Caspy, Andriko von Kügelgen, Elad Stolovicki, Sinead Nguyen, Inés Lucía Patop, Thiberio Rangel, Sebastian Kadener, Lars D. Renner, Vera Thiel, Yoav Soen,  Tanmay A.M. Bharat, Vikram Alva,  Alex Bisson

| Genes & genomes

Early zygotic engineering promotes targeted large transgene integration and direct production of fully transgenic animals

 Khusali Gupta, Ping Xu, Judith Gallant, Yeonsoo Yoon, Jaime A. Rivera-Pérez,  Jeanne B. Lawrence

doi: https://doi.org/10.1101/2024.09.29.615605

Epigenome profiling identifies H3K27me3 regulation of extra-cellular matrix composition in human corticogenesis

 Nora Ditzer, Ezgi Senoglu,  Theresa M. Schütze, Aikaterina Nikolaidi,  Annika Kolodziejczyk,  Katrin Sameith, Sevina Dietz,  Razvan P. Derihaci, Cahit Birdir,  Anne Eugster,  Mike O. Karl,  Andreas Dahl, Pauline Wimberger, Franziska Baenke,  Claudia Peitzsch,  Mareike Albert

Single-cell RNA-seq Reveals Early Transcriptional Programs of the Maternal to Zygote Transition in Mice and Rats

Yangqi Su, Evguenia Kouranova, Jonathan Shea, Xiaoxia Cui,  Zhengchang Su

Tissue-specific transcriptomics uncovers novel craniofacial genes underlying jaw divergence in specialist pupfishes

 M. Fernanda Palominos, Vanessa Muhl,  Christopher H. Martin

Catalytic-dependent and independent functions of the histone acetyltransferase CBP promote pioneer factor-mediated zygotic genome activation

 Audrey J. Marsh,  Sergei Pirogov, Abby J. Ruffridge, Suresh Sajwan, Tyler J. Gibson, George Hunt, Yadwinder Kaur,  Melissa M. Harrison,  Mattias Mannervik

Distinct proliferative and neuronal programmes of chromatin binding and gene activation by ASCL1 are cell cycle stage-specific

 William F Beckman, Lydia M Parkinson, Lewis Chaytor,  Anna Philpott

A piRNA regulating oogenesis and embryo development in cockroaches

 Judit Gonzalvo,  Nuria Farrus,  Jorge Escudero,  David Pujal,  Josep Bau,  Maria-Dolors Piulachs

Deciphering gene regulatory programs in mouse embryonic skin through single-cell multiomics analysis

Qiuting Deng, Pengfei Cai, Yingjie Luo, Zhongjin Zhang, Wen Ma, Zijie Huang, Xiaoya Chen, Shijie Hao, Weiguang Ma, Jiangshan Xu, Mengnan Cheng, Xiumei Lin, Ru Zhou, Shanshan Duan, Junjie Chen, Ronghai Li, Xuyang Shi, Chang Liu, Peng Gao, Jianting Li, Jun Xie, Longqi Liu, Yue Yuan, Chuanyu Liu

Optical Genome Mapping of the human reference iPSC line KOLF2.1J reveals new smaller structural variants in neurodevelopmental genes

 Madison James Yang,  Kamilla Sedov,  Max Y. Chen,  Faria Zafar,  Birgitt Schüle

Setdb1 regulates proper differentiation of adult intestinal stem cells via restraining permissive chromatin structure and transcriptional variability

Dimitris Botskaris, Ioannis K. Deligiannis, Ioanna Peraki, Haroula Kontaki, Marianna Stagaki, Matthieu D. Lavigne,  Celia P. Martinez-Jimenez,  Iannis Talianidis

Loss of Bicra/Gltscr1 leads to a defect in fetal liver macrophages responsible for erythrocyte maturation in mice

Surbhi Sood, Aktan Alpsoy, Guanming Jiao, Alisha Dhiman, Charles Samuel King, Gabriella Grace Conjelko, Judy E. Hallett, Sagar M Utturkar, Jill E Hutchcroft,  Emily C Dykhuizen

Rewired gene interactions during development of serially homologous appendages in male and female Drosophila

Amber M. Ridgway, Javier Figueras Jimenez, Maria D. S. Nunes,  Alistair P. McGregor

Contextualising transcription factor binding during embryogenesis using natural sequence variation

 Olga M. Sigalova,  Mattia Forneris,  Frosina Stojanovska,  Bingqing Zhao,  Rebecca R. Viales, Adam Rabinowitz, Fayrouz Hamal,  Benoît Ballester,  Judith B Zaugg,  Eileen E.M. Furlong

PWWP-ADD and N-terminal domains of DNMT3B1 confer specificity for developmentally regulated CpG island methylation

 Komal Yasmin,  Tatyana B Nesterova,  Neil Brockdorff

Drosophila Trus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis

Saeko Takada, Bonnie J. Bolkan, MaryJane O’Connor, Michael Goldberg,  Michael B. O’Connor

Single-nucleus transcriptional and chromatin accessibility analyses of maturing mouse Achilles tendon uncover the molecular landscape of tendon stem/progenitor cells

Hiroki Tsutsumi,  Tomoki Chiba, Yuta Fujii, Takahide Matsushima, Tsuyoshi Kimura, Akinori Kanai, Akio Kishida, Yutaka Suzuki,  Hiroshi Asahara

Foxn3 is part of a transcriptional network that regulates cilia genes in the developing mouse retina

 Huanqing Zhang,  Fan Meng,  David L. Turner

Spatiotemporal dynamics and selectivity of mRNA translation during mouse pre-implantation development

Hao Ming, Rajan Iyyappan, Kianoush Kakavand, Michal Dvoran, Andrej Susor,  Zongliang Jiang

| Stem cells, regeneration & disease modelling

Axolotl epigenetic clocks offer insights into the nature of negligible senescence

Yuliia Haluza,  Joseph A. Zoller, Ake T. Lu, Hannah E. Walters, Martina Lachnit, Robert Lowe, Amin Haghani, Robert T. Brooke, Naomi Park,  Maximina H. Yun,  Steve Horvath

Lgl resets Par complex membrane loading at mitotic exit to polarize neural stem cells

Bryce LaFoya, Sarah E. Welch,  Kenneth E. Prehoda

RO8191, a new compound for initiating embryo implantation in mice

Junlan Shu, Jumpei Terakawa, Satoko Osuka, Ayako Muraoka, Jiali Ruan, Junya Ito, Atsuo Iida,  Eiichi Hondo

Liver Sinusoidal Endothelial Cells and Laminin dictate cholangiocytes’ fate in chronic liver disease

 Rita Manco, Camilla Moliterni, Gauthier Neirynck, Maxime De Rudder, Corinne Picalausa, Leana Ducor, Montserrat Fraga, Frédéric Lemaigre, Christine Sempoux, Alexandra Dili, Isabelle A. Leclercq

Branched actin polymerization drives invasive protrusion formation to promote myoblast fusion during skeletal muscle regeneration

Yue Lu, Tezin Walji, Pratima Pandey, Chuanli Zhou, Christa Whelan Habela, Scott Snapper, Rong Li,  Elizabeth Chen

The Xenopus respiratory system reveals common tetrapod mechanisms for growth, regeneration and healing

Shiri Kult Perry, Nikko-Ideen Shaidani,  Marko E Horb,  Neil Shubin

Injury-induced transcription in the planarian outer epithelium is critical for tissue regeneration

Pallob Barai, Mariya S. Kibtiya, Nathan G. Maggard, Shishir Biswas,  Elizabeth M. Duncan

Coordinate post-transcriptional regulation by microRNAs and RNA binding proteins is critical for early embryonic cell fate decisions

 Carolyn Sangokoya,  Robert Blelloch

Female-germline specific protein Sakura interacts with Otu and is crucial for germline stem cell renewal and differentiation and oogenesis

Azali Azlan, Li Zhu,  Ryuya Fukunaga

A post-mitotic in vitro murine as a model of muscle damage and repair

Angelo Galluccio, Samantha Maurotti, Francesca Rita Noto, Francesca Scionti, Carmelo Pujia, Elisa Mazza, Yvelise Ferro,  Rosario Mare, Nadia Geirola,  Bernadette Scopacasa,  Patrizio Candeloro,  Luca Tirinato, Angela Sciacqua, Arturo Pujia,  Stefano Romeo, Tiziana Montalcini

Loss of 18q alters TGFβ signalling affecting anteroposterior neuroectodermal fate in human embryonic stem cells

Yingnan Lei, Mai Chi Duong,  Nuša Krivec,  Charlotte Janssens,  Marius Regin,  Anfien Huyghebaert,  Edouard Couvreu de Deckersberg,  Karen Sermon, Diana Al Delbany,  Claudia Spits

Dissecting compounded hepatocyte injury in a model of MASLD progression from human induced pluripotent stem cells

Julian Weihs, Fatima Baldo, Alessandra Cardinali, Gehad Youssef, Katarzyna Ludwik, Harald Stachelscheid, Nils Haep, Peter Tang, Igor Sauer, Pavitra Kumar, Cornelius Engelmann, Susanna Quach, Philip Bufler, Namshik Han, Milad Rezvani

Nicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway

Ryosuke Isotani,  Masaki Igarashi, Masaomi Miura, Kyoko Naruse, Satoshi Kuranami, Manami Katoh, Seitaro Nomura, Toshimasa Yamauchi

Fetal Liver-like Organoids Recapitulate Blood-Liver Niche Development and Multipotent Hematopoiesis from Human Pluripotent Stem Cells

Milad Rezvani, Kyle Lewis, Susanna Quach, Kentaro Iwasawa, Julian Weihs, Hasan Al Reza, Yuqi Cai, Masaki Kimura, RanRan Zhang, Yuka Milton, Praneet Chaturvedi, Konrad Thorner, Ramesh C. Nayak, Jorge Munera, Phillip Kramer, Brian R. Davis, Appakalai N. Balamurugan, Yeni Ait Ahmed, Marcel Finke, Rose Yinghan Behncke, Adrien Guillot, René Hägerling, Julia K. Polansky, Philip Bufler, Jose A Cancelas, James M. Wells, Momoko Yoshimoto,  Takanori Takebe

STAT3 signalling enhances tissue expansion during postimplantation mouse development

Takuya Azami, Bart Theeuwes, Mai-Linh N Ton, William Mansfield, Luke Harland, Masaki Kinoshita,  Berthold Gottgens,  Jennifer Nichols

Single-cell and in situ spatial analyses reveal the diversity of newly born hematopoietic stem cells and of their niches

 Léa Torcq, Catherine Vivier, Sandrine Schmutz,  Yann Loe-Mie,  Anne A. Schmidt

A limbal stem cell deficiency murine model with residual limbal stem cells

Hideaki Someya,  Shintaro Shirahama, Margarete M. Karg, Meredith S. Gregory-Ksander, Reza Dana,  Bruce R. Ksander

Functional differentiation of Human Dental Pulp Stem Cells into neuron-like cells exhibiting electrophysiological activity

 B. Pardo-Rodríguez,  A.M. Baraibar,  I. Manero-Roig,  J. Luzuriaga,  J. Salvador-Moya,  Y. Polo,  R. Basanta-Torres,  F. Unda,  S. Mato,  G. Ibarretxe,  J.R. Pineda

Actomyosin Contractility is a Potent Suppressor of Mesoderm Induction by Human Pluripotent Stem Cells

 Loic Fort, Wenjun Wang,  Ian Macara

map3k1 suppresses terminal differentiation of migratory eye progenitors in planarian regeneration

 Katherine C. Lo,  Christian P. Petersen

Local control of cellular proliferation underlies neuromast regeneration in zebrafish

 Natalia G. Lavalle,  Jerónimo Miranda-Rodríguez,  Emanuel Cura Costa,  Augusto Borges,  Oriol Viader-Llargués, Hernán López-Schier,  Osvaldo Chara

Integrated local and systemic communication factors regulate nascent hematopoietic progenitor escape during developmental hematopoiesis

Carson Shalaby, James Garifallou,  Christopher S Thom

The PUF RNA-binding protein, FBF-2, maintains stem cells without binding to RNA

 Brian H. Carrick,  Sarah L. Crittenden,  MaryGrace Linsley,  Stephany J. Costa Dos Santos,  Marvin Wickens,  Judith Kimble

The E3 Ubiquitin Ligase Trip12 attenuates Wnt9a/Fzd9b signaling during hematopoietic stem cell development

Jessica Ensing, Amber D. Ide, Carla Gilliland, Visakuo Tsurho, Isabella Caza,  Amber N. Stratman, Nathan J. Lanning,  Stephanie Grainger

| Plant development

A molecular basis for plant SCAR/WAVE functional divergence

 Sabine Brumm,  Aleksandr Gavrin,  Matthew Macleod,  Guillaume Chesneau, Annika Usländer,  Sebastian Schornack

Proline-2’-deoxymugineic acid (PDMA) increases seed quality and yield by alleviating iron deficiency symptoms in soybean under calcareous-alkaline conditions

 Zahit Kaya,  Amir Maqbool,  Motofumi Suzuki,  Emre Aksoy

Stochastic Gene Expression in Auxin Signaling in the Floral Meristem of Arabidopsis thaliana

 Shuyao Kong,  Mingyuan Zhu,  Adrienne H.K. Roeder

NPF4.1 imports embryo-derived GA4 to the endosperm to promote seed germination

Mathilde Sirlin-Josserand, Lali Sakvarelidze-Achard, David Pflieger, Jean-Michel Davière,  Patrick Achard

Co-cultivating rice plants with Azolla filiculoides modifies root architecture and timing of developmental stages

Sara Cannavò,  Chiara Paleni,  Alma Costarelli,  Maria Cristina Valeri,  Martina Cerri,  Antonietta Saccomanno,  Veronica Gregis,  Graziella Chini Zittelli,  Petre I. Dobrev,  Lara Reale, Martin M. Kater,  Francesco Paolocci

The genetic basis of replicated bullseye pattern reduction across the Trionum Complex

 May T. S. Yeo, Alice L. M. Fairnie, Valentina Travaglia, Joseph F. Walker,  Lucie Riglet, Selin Zeyrek,  Edwige Moyroud

PRC2 facilitates the transition from heterotrophy to photoautotrophy during seedling emergence

 Naseem Samo,  María Guadalupe Trejo-Arellano,  Lenka Gahurová, Alexander Erban,  Alina Ebert,  Quentin Rivière,  Jiří Kubásek,  Fatemeh Aflaki,  Helena Hönig Mondeková,  Armin Schlereth,  Annick Dubois,  Mingxi Zhou,  Ondřej Novák,  Jiří Šantrůček,  Daniel Bouyer,  Franҫois Roudier,  Joachim Kopka,  Iva Mozgová

A brassinosteroid receptor kinase is required for sex determination in the homosporous fern Ceratopteris richardii

 Katelin M. Burow,  Xi Yang,  Yun Zhou,  Brian P. Dilkes,  Jennifer H. Wisecaver

ERECTA family signaling controls cell fate specification during ovule initiation in Arabidopsis

 Alex M. Overholt,  Christina Elaine Pierce, Calen Seth Paleologos,  Elena D. Shpak

Shaping Kale Morphology and Physiology Using Different LED Light Recipes

 Sabine Scandola,  Lauren E. Grubb,  Brigo Castillo,  Lexyn Iliscupidez,  Curtis Kennedy, Nicholas Boyce,  R. Glen Uhrig

Highly expressed cell wall genes contribute to robustness of sepal size

 Diego A. Hartasánchez,  Mathilde Dumond, Nelly Dubrulle,  Françoise Monéger,  Arezki Boudaoud

Differential gene expression analysis identifies a group of defensin like peptides from Solanum chacoense ovules with in vitro pollen tube attraction activity

Yang Liu, Valentin Joly, Mohamed Sabar, Daniel Philippe Matton, David Morse

| Environment, evolution and development

Like mother, like daughter? Phenotypic plasticity, environmental covariation, and heritability of size in a parthenogenetic wasp

Alicia Tovar, Scott Monahan, Trevor Mugoya, Adrian Kristan, Walker Welch, Ryan Dettmers, Camila Arce, Theresa Buck, Michele Ruben, Alexander Rothenberg, Roxane Saisho, Ryan Cartmill, Timothy Skaggs, Robert Reyes, MJ Lee, John Obrycki, William Kristan,  Arun Sethuraman

Methylomes reveal recent evolutionary changes in populations of two plant species

 Kevin Korfmann, Andreas Zauchner,  Aurélien Tellier,  Ramesh Arunkumar

Polar bodies serve as a landmark for anteroposterior axis formation in spiders

Ruixun Wang,  Matthias Pechmann

Evolutionary Insights into Muscle Fiber Distribution in the Twin Tails of Ornamental Goldfish

 Kinya G Ota,  Gembu Abe,  Chen-Yi Wang,  Ing-Jia Li,  Paul Gerald Layague Sanchez,  Tzu-Chin Chi

Maternal high-fat, high-sucrose diet-induced excess adiposity is linked to placental hypoxia and disruption of fetoplacental immune homeostasis in late gestation

 Christian J. Bellissimo, Tatiane A. Ribeiro, Erica Yeo, Patrycja A. Jazwiec, Howard Luo, Jaskiran Bains,  Deborah M. Sloboda

Cenozoic evolutionary history obscures the Mesozoic origins of acanthopterygian fishes

Chase D. Brownstein, Alex Dornburg, Thomas J. Near

Reconstructing the deep phylogeny of the MAPK signaling network: functional specialization via multi-tier coevolutionary expansion

 EJ Huang,  Jeeun Parksong,  Amy F. Peterson,  Fernando Torres,  Sergi Regot,  Gabriel S. Bever

Diversity and evolution of Radiolaria: Beyond the stars of the ocean

 Miguel M. Sandin,  Johan Renaudie, Noritoshi Suzuki,  Fabrice Not

Growth compensation upon changes in tissue size in the Drosophila abdomen

Ana Ferreira, Andrea Cairoli, Federica Mangione, Maxine V. Holder, Anna Ainslie, Birgit L. Aerne,  Guillaume Salbreux,  Nicolas Tapon

Evolution of the non-visual and visual opsin gene repertoire in ray-finned fishes

 Maxime Policarpo,  Lily G. Fogg,  Fabio Cortesi,  Walter Salzburger

The genetic diversity of the soybean rust pathogen Phakopsora pachyrhizi has been driven by two major evolutionary lineages

Vinicius Delgado da Rocha, Everton Geraldo Capote Ferreira, Fernanda Machado Castanho, Marcia Kamogae Kuwahara, Cláudia Vieira Godoy, Maurício Conrado Meyer, Kerry F. Pedley, Ralf T. Voegele, Anna Lipzen, Kerrie Barry, Igor V. Grigoriev, Marco Loehrer, Ulrich Schaffrath, Catherine Sirven,  Sebastien Duplessis,  Francismar Corrêa Marcelino-Guimarães

Phylogeny-aware simulations suggest a low impact of unsampled lineages in the inference of gene flow during eukaryogenesis

 Moisès Bernabeu,  Saioa Manzano-Morales,  Toni Gabaldón

Evolution of plant cell-type-specific cis-regulatory elements

Haidong Yan, John P. Mendieta, Xuan Zhang, Alexandre P. Marand, Yan Liang, Ziliang Luo, Mark A.A. Minow, Hosung Jang, Xiang Li, Thomas Roulé, Doris Wagner, Xiaoyu Tu, Yonghong Wang, Daiquan Jiang, Silin Zhong,  Linkai Huang, Susan R. Wessler,  Robert J. Schmitz

Germplasm stability in zebrafish requires maternal Tdrd6a and Tdrd6c

 Alessandro Consorte, Yasmin El Sherif,  Fridolin Kielisch,  Nadine Wittkopp,  René F. Ketting

Genetic variation in male mate choice for large females in Drosophila melanogaster

Grace S. Freed, Isabella G. Martinez, Avigayil Lev, Ana-Maria Anthony Cuadrado,  Alison Pischedda

Deep-sea fish reveal alternative pathway for vertebrate visual development

 Lily G. Fogg,  Stamatina Isari, Jonathan E. Barnes,  Jagdish Suresh Patel,  N. Justin Marshall,  Walter Salzburger,  Fabio Cortesi,  Fanny de Busserolles

Comparative analysis of rhesus macaque and human placental organoids highlights evolutionary differences in placentation

 Allyson Caldwell,  Liheng Yang,  Elizabeth A. Scheef,  Amitinder Kaur,  Carolyn B. Coyne

Experimental short-term heatwaves negatively impact body weight gain and survival during larval development in a wild pollinator

Laura Wögler,  Christoph Kurze

Male is the default sex: functional significance of the sex determination cascade in horned dung beetles

London C. Mitchell,  Armin P. Moczek,  Erica M. Nadolski

Identification of a specialized lipid barrier for Drosophila metamorphosis

 Lena Lampe,  Clare L. Newell, Bing-Jun Wang, Rami Makki, Cyrille Alexandre,  Ian S. Gilmore,  Li Zhao,  Alex P. Gould

Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene program in bat wing development

Magdalena Schindler, Christian Feregrino, Silvia Aldrovandi, Bai-Wei Lo, Anna A. Monaco, Alessa R. Ringel, Ariadna Morales,  Tobias Zehnder, Rose Yinghan Behncke, Juliane Glaser, Alexander Barclay, Guillaume Andrey, Bjørt K. Kragesteen, René Hägerling, Stefan Haas, Martin Vingron,  Igor Ulitsky, Marc Marti-Renom,  Julio Hechavarria,  Nicolas Fasel, Michael Hiller, Darío Lupiáñez, Stefan Mundlos,  Francisca M. Real

Shaping tiny worlds: Paternal microbiota manipulation influences offspring microbial colonization and development in a sex role-reversed pipefish

 Kim-Sara Wagner, Frédéric Salasc, Silke-Mareike Marten,  Olivia Roth

Single Cell Sequencing Provides Clues about the Developmental Genetic Basis of Evolutionary Adaptations in Syngnathid Fishes

 Hope M. Healey,  Hayden B. Penn,  Clayton M. Small,  Susan Bassham,  Vithika Goyal,  Micah A. Woods,  William A. Cresko

Oxygen level alters energy metabolism in bovine preimplantation embryos

 N. Boskovic,  M. Ivask,  G. Yazgeldi Gunaydin,  B. Yaşar,  S. Katayama,  A. Salumets,  T. Org,  A. Kurg,  K. Lundin,  T. Tuuri,  C. O. Daub,  J. Kere

Hybrid incompatibility emerges at the one-cell stage in interspecies Caenorhabditis embryos

 Jessica Bloom,  Rebecca Green,  Arshad Desai,  Karen Oegema,  Scott A. Rifkin

Evolution of maternal and early zygotic transcript regulation across Drosophila

Charles S. Omura,  Susan E. Lott

Cellular and molecular mechanisms that shape the development and evolution of tail vertebral proportion in mice and jerboas

 Ceri J. Weber,  Alexander J. Weitzel, Alexander Y. Liu,  Erica G. Gacasan,  Robert L. Sah,  Kimberly L. Cooper

Planarians Develop Radiotolerance to Recurrent Ionizing Radiation Exposure

Paul G. Barghouth, Benjamin Ziman, Eli Isael Maciel, Peter Karabinis, Salvador Rojas, Natasha M. Flores, Edelweiss Pfister, Néstor J. Oviedo

Shifts in embryonic oxygen levels cue heterochrony in limb initiation

 Meng Zhu, Rinaldo Catta-Preta, ChangHee Lee, Clifford Tabin

Brassinosteroids and Flavonols Confer Temperature Stress Tolerance to Pollen Tube Germination and Growth

 Kumi Matsuura-Tokita, Ayaka Sakai,  Takamasa Suzuki,  Akihiko Nakano,  Tetsuya Higashiyama

Cell Biology

The multimodal transcriptional response of denervated skeletal muscle involves alterations in cholesterol homeostasis impacting muscle size

Cristofer Calvo, Casey O. Swoboda, Fabian Montecino Morales, Siddhant Nagar, Michael J. Petrany, Chengyi Sun, Hima Bindu Durumutla,  Mattia Quattrocelli,  Douglas P. Millay

The role of cytochrome c in mitochondrial metabolism of human oocytes

 Jakub Maciej Surmacki,  Halina Abramczyk, Bogna Sobkiewicz,  Renata Walczak-Jędrzejowska,  Jolanta Słowikowska-Hilczer,  Katarzyna Marchlewska

The molecular chronology of mammary epithelial cell fate switching

 Queralt Vallmajo-Martin,  Zhibo Ma, Sumana Srinivasan, Divya Murali, Christopher Dravis,  Kavitha Mukund, Shankar Subramaniam,  Geoffrey M. Wahl,  Nikki K. Lytle

Enhanced RNA-targeting CRISPR-Cas technology in zebrafish

 Ismael Moreno-Sanchez, Luis Hernandez-Huertas, Daniel Nahon-Cano, Carlos Gomez-Marin, Pedro Manuel Martinez-García, Anthony J. Treichel, Laura Tomas-Gallardo, Gabriel da Silva Pescador, Gopal Kushawah, Alejandro Díaz-Moscoso, Alejandra Cano-Ruiz, John A. Walker II, Manuel J. Muñoz, Kevin Holden, Joan Galcerán, María Ángela Nieto, Ariel Bazzini,  Miguel A. Moreno-Mateos

Intra-manchette transport employs both microtubule and actin tracks

Jo H. Judernatz, Laura Pérez Pañeda, Tereza Kadavá,  Albert J. R. Heck,  Tzviya Zeev-Ben-Mordehai

Visualizing developmental dynamics of nuclear morphology and transport machinery in Drosophila

 Yuki Shindo, Shruthi Balachandra,  Amanda A. Amodeo

Mammary Epithelial Migration is EMT-Independent

Jing Chen, Rongze ma, Zhixuan Deng, Yunzhe Lu, Jiecan Zhou, Kun Xia, Ophir D. Klein, Pengfei Lu

An interkinetic envelope surrounds chromosomes between meiosis I and II in C. elegans oocytes

Layla El Mossadeq, Laura Bellutti, Rémi Le Borgne, Julie C. Canman,  Lionel Pintard, Jean-Marc Verbavatz,  Peter Askjaer, Julien Dumont

Depolymerizing F-actin accelerates the exit from pluripotency to enhance stem cell-derived islet differentiation

Nathaniel J. Hogrebe, Mason D. Schmidt, Punn Augsornworawat, Sarah E. Gale, Mira Shunkarova,  Jeffrey R. Millman

Autophagy is dispensable in germline stem cells but is required in the cap cells for their maintenance in the Drosophila ovarian niche

Kiran Suhas Nilangekar,  Bhupendra V. Shravage

Mitochondrial fission controls astrocyte morphogenesis and organization in the cortex

Maria Pia Rodriguez Salazar, Sprihaa Kolanukuduru, Valentina Ramirez, Boyu Lyu, Gabrielle Sejourne, Hiromi Sesaki, Guoqiang Yu,  Cagla Eroglu

Impaired erythroid maturation in murine embryos upon loss of the preeclampsia-associated serine protease prostasin

 Sara Di Carlo, Adrian Salas-Bastos, Mariela Castelblanco Castelblanco, Muriel Auberson, Marie Rumpler, Malaury Tournier, Lukas Sommer, Olaia Naveiras, Edith Hummler

Membrane oscillations driven by Arp2/3 constrict the intercellular bridge during neural stem cell divisions

Bryce LaFoya,  Kenneth E. Prehoda

eIF4ET regulates meiotic proteome levels to enable oocyte formation and storage

Priyankaa Bhatia, Ruchi Amin, Nicole E. Familiari, Kan Yaguchi, Vanna M. Tran, Alec Bond, Orhan Bukulmez, Jeffrey B. Woodruff

Human spermatogenesis leads to a reduced nuclear pore structure and function

Ália dos Santos, Oliver Knowles, Tom Dendooven, Thomas Hale, Alister Burt, Piotr Kolata, Giuseppe Cannone, Dom Bellini,  David Barford, Matteo Allegretti

Modelling

Uniaxial force modifies the length of the mammary ductal network and the orientation of ducts during pubertal development: Findings from computational modeling and laboratory experiments

Daisy Ulloa, Kelsey M. Temple,  Theresa M. Casey, Uduak Z George

Quantitative Resolving Cell Fate in the Early Embryogenesis of Caenorhabditis elegans

 Ruiqi Xiong, Yang Su,  Mengchao Yao, Zefei Liu, Jie Lu, Yong-Cong Chen, Ping Ao

Inner ear morphology in wild versus laboratory house micev

Sabrina Renaud, Léa Amar, Pascale Chevret, Caroline Romestaing, Jean-Pierre Quéré, Corinne Régis, Renaud Lebrun

Optimal network sizes for most robust Turing patterns

Hazlam S. Ahmad Shaberi, Aibek Kappassov, Antonio Matas-Gil, Robert G. Endres

Parsing altered brain connectivity in neurodevelopmental disorders by integrating graph-based normative modeling and deep generative networks

Rui Sherry Shen, Yusuf Osmanlıoğlu, Drew Parker, Darien Aunapu, Benjamin E. Yerys, Birkan Tunç, Ragini Verma

Optimizing Non-Intersecting Synthetic Vascular Trees in Nonconvex Organs

Etienne Jessen, Marc C. Steinbach, Dominik Schillinger

Tools & Resources

Unbiased identification of cell identity in dense mixed neural cultures

 Sarah De Beuckeleer, Tim Van De Looverbosch, Johanna Van Den Daele, Peter Ponsaerts,  Winnok H. De Vos

A MOUSE ORGANOID PLATFORM FOR MODELING CEREBRAL CORTEX DEVELOPMENT AND CIS-REGULATORY EVOLUTION IN VITRO

 Daniel Medina-Cano, Mohammed T. Islam, Veronika Petrova, Sanjana Dixit, Zerina Balic, Marty G. Yang, Matthias Stadtfeld,  Emily S. Wong,  Thomas Vierbuchen

A stable Netrin-1 fluorescent reporter chicken reveals cell-specific molecular signatures during optic fissure closure

Brian Ho Ching Chan,  Holly Hardy,  Teresa Requena, Amy Findlay,  Jason Ioannidis, Dominique Meunier,  Maria Toms,  Mariya Moosajee, Anna Raper,  Mike McGrew,  Joe Rainger

A minimally guided organoid model for cross-species comparisons of cerebellar development

 Luca Guglielmi, Daniel Lloyd-Davies-Sánchez,  José González Martínez,  Madeline A. Lancaster

CellStudio: a Modular, Tunable and Accessible Platform for Analysis of Growth Factors Secretions in Cell Cultures

 Enrique Azuaje-Hualde,  Naiara Lartitegui-Meneses,  Juncal Alonso-Cabrera,  Asier Inchaurraga-Llamas,  Yara Alvarez-Braña,  Marian Martínez de Pancorbo,  Fernando Benito-Lopez,  Lourdes Basabe-Desmonts

A Combined Computational Fluid Dynamics Modeling and Geometric Morphometrics Methods Approach to Quantifying Hemodynamic and Anatomical Features of Embryonic Chick Heart Anatomies Reconstructed from Light Sheet Fluorescence Microscopy Imaging

 Kirsten Giesbrecht, Simone Rossi, Sophie Liu, Shourya Mukherjee,  Michael Bressan,  Boyce Griffith

CellMet: Extracting 3D shape metrics from cells and tissues

 Sophie Theis,  Mario A Mendieta-Serrano,  Bernardo Chapa-y-Lazo, Juliet Chen,  Timothy E Saunders

CRISPR/Cas9-based somatic knock-in of reporters in the avian embryo in ovo

Alciades Petit Vargas, Baptiste Mida, Rosette Goïame, Olinda Alegria-Prevot, Bojana Djelic,  Evelyne Fischer,  Samuel Tozer,  Jérôme Gros,  Marie Manceau,  Xavier Morin

From Selfies to Science – Precise 3D Leaf Measurement with iPhone 13 and Its Implications for Plant Development and Transpiration

 Gabriel Bar-Sella,  Matan Gavish,  Menachem Moshelion

Zebrahub-Multiome: Uncovering Gene Regulatory Network Dynamics During Zebrafish Embryogenesis

 Yang Joon Kim,  Shruthi Vijay Kumar,  Benjamin Iovino,  Alejandro Granados,  Sarah Ancheta,  Xiang Zhao,  Kyle Awayan, Amanda Seng,  Michael Borja,  Sheryl Paul,  Honey Mekonen, Ritwicq Arjyal,  Angela Detweiler,  Yasin Şenbabaoğlu,  Rafael Gómez-Sjöberg,  Norma Neff,  Merlin Lange,  Loïc A. Royer

inTRACKtive — A Web-Based Tool for Interactive Cell Tracking Visualization

 Teun A.P.M. Huijben,  Ashley G. Anderson III,  Andrew Sweet, Erin Hoops, Connor Larsen,  Kyle Awayan,  Jordão Bragantini, Chi-Li Chiu,  Loïc A. Royer

Enrichment of spermatogonial stem cells and staging of the testis cycle in a dasyurid marsupial, the fat-tailed dunnart

 Gerard A. Tarulli, Patrick R.S. Tatt, Rhys Howlett, Sara Ord, Beth Shapiro, Stephen R. Frankenberg,  Andrew J. Pask

Defining Cellular Diversity at the Swine Maternal-Fetal Interface Using Spatial Transcriptomics and Organoids

 Cole R. McCutcheon,  Allyson Caldwell,  Liheng (Henry) Yang,  Elisa Crisci,  J. Alex Pasternak,  Carolyn B. Coyne

Generation of human iPSC-derived pancreatic organoids to study pancreas development and disease

Jean-Francois Darrigrand, Abigail Isaacson,  Francesca M. Spagnoli

Spatiotemporal map of the developing human reproductive tract at single-cell resolution

 Valentina Lorenzi, Cecilia Icoresi Mazzeo, Nadav Yayon, Elias R. Ruiz-Morales, Carmen Sancho-Serra, Frederick C.K. Wong, Magda Marečková, Liz Tuck, Kenny Roberts, Tong Li, Marc-Antoine Jacques, Xiaoling He, Roger Barker, Berta Crespo, Batuhan Cakir, Simon Murray, Martin Prete, Yong Gu, Iva Kelava,  Luz Garcia Alonso,  John C Marioni,  Roser Vento Tormo

Research practice & education

Distinct patterns of bioscience doctoral publication disparities by gender and race/ethnicity

Katie Leap, Gregory S. Payne, Janet S. Sinsheimer,  Diana E. Azurdia

Features and signals in precocious citation impact: a meta-research study

 John P.A. Ioannidis

Equity in Action: A Four-Year journey towards Gender Parity and Racial Diversity in Biochemistry Hiring

 Sherri L. Christian,  Valerie Booth,  Scott Harding,  Amy M. Todd,  Mark D. Berry

LeDNA: a cut-and-build toolkit to democratize education on CRISPR gene editing technology

 Guilherme E. Kundlatsch,  Alina S. L. Rodrigues,  Vitória F. B. Zocca,  Laura A. S. Amorim,  Gabriela B. de Paiva,  Almiro P. S. Neto,  Juliana A. D. B. Campos,  Danielle B. Pedrolli

Artificial Intelligence’s Contribution to Biomedical Literature Search: Revolutionizing or Complicating?

 Rui Yip, Young Joo Sun, Alexander G. Bassuk, Vinit B. Mahajan

Quantifying Data Distortion in Bar Graphs in Biological Research

 Teng-Jui Lin,  Markita P. Landry

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The 30 October 2024 Development presents… webinar was chaired by Development’s Executive Editor, Katherine Brown and featured three talks on the topic of the development of ectoderm derivatives. Catch up on the talks below.

Eirini Maniou (University of Padua)

Daniel Aldea (Aix-Marseille University)

Casey Griffin (New York University)

(2 votes)
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During my time as a summer student at the Francis Crick Institute, I had the privilege of working in the Developmental Signalling Laboratory of Dr Caroline Hill. Under the mentorship of Dr Berta Font Cunill, I have gained an insight into the realities of cutting-edge scientific research and was able to contribute to experiments advancing the understanding of developmental biology.

Throughout embryonic development, as cells divide, they begin to specialise to later form diverse functional tissues. This is possible because, even though progenitor cells contain copies of the same genetic code, they express different sets of genes. These gene expression patterns are governed by various complex signalling pathways, which ultimately determine cell fate. The Hill Lab is interested in understanding how cells use specific signals to communicate with each other and their environment to drive the development of an organism and tissue specialisation. During gastrulation, this cellular communication results in the embryonic stem cells transforming into three distinct germ layers: endoderm, mesoderm, and ectoderm. As their subsequent patterning generates all future body structures, this process sets the stage for the functioning of the entire organism (Richardson et al., 2023).

In my research project, I was specifically interested in the mechanism of cell differentiation into definitive endoderm. This germ layer gives rise to the lungs, bladder, the majority of the digestive tract, as well as vital endocrine organs like the pancreas and thyroid (Fang & Li, 2022). Understanding the signalling pathways involved in endoderm differentiation is necessary to generate novel therapeutic solutions to diseases associated with endoderm-derived tissues, such as diabetes. This is possible by using human induced pluripotent stem cells (iPSCs) to generate endodermal cells, and possibly their derivatives, in vitro (Fang & Li, 2022).

To study the differentiation to endoderm, I cultured iPSCs for four days in differentiation media with addition of CHIR-99021 (5 µM) for 24h, and Activin A (20 ng/mL) for 72h, following a standard protocol (Fig. 1a). Based on previous publications (Diekmann and Naujok, 2015), I expected that throughout this process, cells would follow certain patterns of gene expression (Fig. 1b). After 72h of differentiation (Day 4), I fixed and stained the cells with antibodies recognising key markers of pluripotency (Oct4) and endoderm (Sox17). I imaged the cells (Fig. 1c), quantified the results and was able to establish that the protocol of interest results in about 80% of stem cells differentiating to endoderm cells (Fig. 1d), confirming what has been observed in published articles.

Having established the standard differentiation protocol, I wanted to understand the process itself in more detail. I set out to investigate the gene expression patterns throughout the transition of cells from pluripotency to endoderm. I collected cell samples on each day of the protocol. After extracting RNA, I synthesised cDNA to be used in quantitative polymerase chain reaction (qPCR) analysis. qPCR allows for the amplification of target DNA sequences, with simultaneous quantification of their concentration throughout the process. Thus, I was able to obtain and visualise the levels of expression of endoderm differentiation marker genes on each day of the protocol (Fig. 2). I was able to prove that cells transitioning from pluripotency to endoderm follow predicted patterns of gene expression (Fig. 1b). Pluripotency genes (POU5F1, SOX2) gradually decline as the differentiation continues (Fig. 2a), while endoderm markers (SOX17, GSC) are expressed more substantially towards the end of the process (Fig. 2c). I was also able to confirm that the cells go through an intermediate stage, with mesendoderm genes (TBXT, MIXL1) being expressed transiently on Day 2 (Fig. 2b).

To better understand the signalling pathways involved in the process of cell differentiation to endoderm, Dr Berta Font Cunill screened a library of over 1,000 small molecules of diverse molecular structure that could possibly affect the process by interacting with proteins important for endoderm differentiation. She identified one small molecule (compound “953”) that increases the differentiation efficiency to endoderm (from 80 to 90% approximately).

As I previously mentioned, after following the standard protocol the rate of differentiation to endoderm cells reaches about 80% (Fig. 1d). This high efficiency leaves a small margin for improvement. My goal was to modify the standard differentiation protocol to achieve a lower differentiation efficiency, and therefore increase the margin for improvement upon addition of compound “953”. I seeded pluripotent cells in media with varying concentrations of CHIR-99021 and Activin A (Fig. 3) and carried out the differentiation protocol for three days. I observed that even when the amount of Activin A was lowered from 20 ng/mL to 4 ng/mL, the differentiation proceeded only with minor changes in efficiency (Fig. 3a). However, lowering the amount of CHIR-99021 in just 1 µM increments hindered the process considerably (Fig. 3b). When CHIR-99021 was not present at all, most cells didn’t survive. These results show that CHIR-99021 is vital for endoderm differentiation.

Based on the obtained results, I decided that the best condition to test the effect of compound “953” was 20 ng/mL of Activin A (48h), and 3 µM of CHIR-99021 (24h), which resulted in around 50% of differentiation efficiency, leaving a large margin for improvement. I cultured the cells for three days using these new conditions and different concentrations of compound “953”, after which I stained for Oct4 and Sox17 (Fig. 4). I observed that cells grown with 10 µM of compound “953” in the media, reached 10-15% higher differentiation efficiency than those grown without the compound (Fig. 4a). However, the final total number of cells was lower than in control groups (Fig. 4b). These results suggest that while molecule “953” pushes differentiation from pluripotency into endoderm cells, it is also possibly mildly toxic or hinders cell proliferation. The results also suggest that even if differentiation is hindered, compound “953” is not able to increase the differentiation efficiency beyond 10-15%.

The future of this project will focus on identifying the protein impacted by compound “953” through extensive proteomic analysis. This will allow for a better understanding of the signalling pathways involved in cell differentiation to definitive endoderm, which is a necessary step for the successful differentiation of downstream endoderm-derived tissues and organs to develop novel solutions in regenerative medicine. I am incredibly grateful for the opportunity to contribute to such inspiring scientific advancements. It has been an honour to be supported by the Rosa Beddington Fund. This experience has been a defining moment for my academic and professional development, and I have made the decision to pursue similar research through a PhD studentship and the rest of my scientific career. I would like to thank the Hill Lab, where I had the pleasure of working with incredible scientists, for their support and for welcoming me as a valued team member. I am especially grateful for the guidance and expertise of my supervisor, Dr Berta Font Cunill.

SOURCES

Diekmann, U., Naujok, O. (2015). Generation and Purification of Definitive Endoderm Cells Generated from Pluripotent Stem Cells. Methods in Molecular Biology, 1341, 157-72. https://doi.org/10.1007/7651_2015_220 

Fang, Y., Li, X. (2022). Metabolic and epigenetic regulation of endoderm differentiation. Trends in Cell Biology, 32(2), 151-164. https://doi.org/10.1016/j.tcb.2021.09.002 

Richardson, L., Wilcockson, S.G., Guglielmi, L. et al. (2023). Context-dependent TGFβ family signalling in cell fate regulation. Nature Reviews Molecular Cell Biology, 24, 876–894. https://doi.org/10.1038/s41580-023-00638-3 

Silva, I.B.B., Kimura, C.H., Colantoni, V.P. et al. (2022). Stem cells differentiation into insulin-producing cells: recent advances and current challenges. Stem Cell Research & Therapy, 13, 309. https://doi.org/10.1186/s13287-022-02977-y 

Zhao, M., Tang, Y., Zhou, Y. et al. (2019). Deciphering Role of Wnt Signalling in Cardiac Mesoderm and Cardiomyocyte Differentiation from Human iPSCs: Four-dimensional control of Wnt pathway for hiPSC-CMs differentiation. Nature Scientific Reports, 9, 19389. https://doi.org/10.1038/s41598-019-55620-x

(10 votes)
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[This post is co-written by Joan-Josep Soto Angel and Pawel Burkhardt.]

What is this?

The video depicts the process of reverse development in the ctenophore Mnemiopsis leidyi over several weeks. Adult and larval M. leidyi are anatomically different: lobate adults have lobes and auricles that are not yet developed in the larval stage. Cydippid larvae have a rounded body and tentacles that get reabsorbed during the lobate adult stage. The timelapse video shows an adult comb jelly slowly transitioning to a larval form over time, with lobes and auricles disappearing, and tentacles being regained. This is a process called reverse development.

Where can this be found?

This footage was obtained in our Ctenophore Facility at the University of Bergen, under controlled laboratory conditions, and following the same individual over time. Whether or not these comb jellies are equally capable of doing this in the ocean still remains a mystery, but the potential is definitely there!

Read more about our Ctenophore Facility at Michael Sars Centre here: https://www.uib.no/en/michaelsarscentre/122963/ctenophora-facility

How was this taken?

The timelapse is made out of 24 individual pictures, each taken every 2-3 days, and shows the animal in the same position for comparison purposes. We used a Canon 5D Mark IV coupled to a Canon MP-E 65mm f/2.8 1-5x Macro Photo, usually known as an extreme macro lens. As the animals are very transparent, and the details are difficult to observe, we used a black background and added an extra light source from the side using a Canon speedlite strobe.

What causes M. leidyi to reverse develop?

Reverse development in M. leidyi is triggered by improved environmental conditions after a period of stress. Stress was simulated by either removing the lobes (lobectomy) or by prolonged starvation. Mnemiopsis leidyi is able to efficiently regenerate any missing body part, as well as shrinking considerably when starved. However, when adequately fed after shrinking to a size of just a few millimetres, instead of growing back the lobes, they grew tentacles typical of the larval stage.

Why should people care about this?

So far, reverse development was thought to be restricted to a few cnidarian species and one cestode. Our study is the first to report the occurrence of this peculiar feature in ctenophores, suggesting that reverse development may be more widespread than previously thought. The occurrence of reverse development in a lineage that originated prior to cnidarians can help to better understand central aspects of life cycle plasticity and evolution in early animals. The ability to rejuvenate in harsh conditions also provides further research opportunities for ecological studies aiming to explain, among others, the high invasive success of this comb jelly. Our study highlights Mnemiopsis leidyi as a potential model species to study life cycle plasticity, aging and rejuvenation.

How would you explain this to an 8-year-old?

Aging is a one-way route for a great majority of animals. However, there are a few that seem to be able to escape the fate of getting old. An adult transforming into a baby was only known for a species of jellyfish, usually called the immortal jellyfish (its scientific name is Turritopsis dorhnii). We found this capacity in an entirely new group of animals: the comb jellies. When Mnemiopsis leidyi (also known by its common name as sea walnut) becomes an adult, it grows two lobes and four pointy finger-like structures called auricles that they use for feeding. Baby sea walnuts do not have these body parts. Instead, they use two long tentacles to trap their prey and direct it to the mouth. The tentacles are lost once these animals reach their final adult form. We discovered that adult sea walnuts can rejuvenate when they eat properly after going through a period of stress.

Where can people find more about it?

You can find more information about our finding in the link here: https://www.pnas.org/doi/10.1073/pnas.2411499121

(1 votes)
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