We recently caught up with Delan Alasaadi, who received the 2024 British Society for Developmental Biology (BSDB) Beddington Medal for the best PhD thesis in developmental biology defended in the year previous to the award. Delan gave a talk about his PhD work at the joint BSDB/ Genetics Society Spring Meeting in Warwick in April 2024, and was presented with the Beddington Medal.
Where were you born, and where did you grow up?
I started school in Baghdad, Iraq, where I was born, and continued my studies in Amman, Jordan. My next academic adventure was in Lebanon, where I did my undergraduate degree at the American University of Beirut (AUB).
When did you first become interested in science?
I first became interested in science during my early teenage years. My curiosity about the world around me was growing by the day, and I was constantly puzzled about a wide range of questions like: Where do ideas come from?How can we stimulate more? And how can we decide which notions to follow and which to let go of? Too many questions that involve too many fields like psychology, sociology, science, and more. The underlying theme, regardless of the topic, was this passion for questioning and the attempt to find answers, which became a driving force in my life beyond my “working” hours. The word working is highlighted because if you have an interest in exploring what is around you, beyond your Petri dish or animal model, then do you ever stop?
One direct influence on this way of thinking was the movie “A Beautiful Mind,” which I watched when I was about 15 years old. Avoiding spoiling this marvel of a movie, it initially had a grip on me for eliciting how appealing the outcome of being a scientist was. As I continued my education, this blend of curiosity and inspiration from stories like Nash’s (the main character) drove me to explore various fields of science. Certainly, years later, my view of the movie’s ending changed, and I came to the realization of the importance of grit in the pursuit of what is meaningful knowledge over what is expedient despite obstacles. This mindset has stayed with me, fuelling my continuous quest for knowledge and my love for science.
How did you come to do a PhD with Roberto Mayor at University College London (UCL)?
My undergraduate degree was in biomedical sciences, and my master’s degree at the University of Chester was in differentiation and de-differentiation of macrophages. Despite enjoying doing both, I constantly was asking How (in what) I would develop a niche? And What does that question really constitute? It is easier, saying to myself, to start in a new or emerging field because there is a lot to discover – no matter what, I’ll make it. I was completely wrong, yet the outcome of this approach worked great. That thinking made me choose to explore how physical forces influence the biological behavior of cells. With that interest, the city, and the diverse expertise and pivotal discoveries in mind, I applied to Roberto’s lab. Roberto and his team, throughout decades, specialized in untangling the physical microenvironment and cell signaling pathways that dictate the induction, migration, and differentiation of neural crest cells. The lab has access to a wide range of animal models, cell lines, and biophysical tools, which meant the only limitation was the questions I would ask. I was stunned in my first meeting with Roberto, where we had a well-rounded, simple, down to earth conversation about the possibility of me joining his team. The freedom to express ideas freely and discuss them constructively is a predisposition to any place I aim to be in – so I joined. One week into my PhD, Roberto taught my first fundamental lesson; he said: “The frog is the boss; we will ask the frog if our question is right or wrong.” I knew I was in the right place to get it done.
Your recent NCB paper summarises your main PhD project on neural crest competence. How did the project get started?
This project started when I was around ten years old. One of Roberto Mayor’s students was investigating the resilience of neural crest cells in a Petri dish. The student put a small glass (coverslip) on top of these cells, and to their surprise, the neural crest cells did not die, yet they did not retain their identity either. Although this was a fascinating result, the cause behind this outcome remained unclear – it got shelved. Two decades later, I joined Roberto’s lab and decided to revisit this phenomenon. The immediate hypothesis was that the coverslip applied pressure to the neural crest cells (a mechanical stimulus), changing their nature and preventing them from retaining their neural crest identity—so many questions to answer and so many avenues we could have taken. One question came right at the top of the list: Does this happen in vivo as well? If so, How does that actually happen? Given that neural crest cells in developing embryos are exposed to hydrostatic pressure generated from a liquid-filled cavity (blastocoel cavity), I explored hydrostatic pressure’s role on neural crest cells, an emerging mechanical stimulus in the field of biophysics.
The work involved a wide range of techniques – do you have a favourite?
It has to be inflation and deflation. These two techniques involved artificially changing the hydrostatic pressure within the blastocoel cavity by changing its volume. We called aspirating fluid from the blastocoel Deflation and adding fluid Inflation. Although these two assays were a challenge to optimize from scratch to suit our model of choice, the Xenopus embryos, I enjoyed them the most, at the end of the day, it felt like inflating or deflating a balloon – it is OK, arguably a must, to stay in touch with your inner child-like exploratory mode.
Were there any frustrating moments?
Sure! I wonder if there is anyone who embarked on a scientific journey without being utterly and completely frustrated. However, throughout my PhD, I approached these challenging moments with a more unbiased mindset and as objective as possible I can be. In these moments, your choice of the “right” environment is vital – you get to pick the premise of what “right” means here. Thus, I often mention it is important to pick an environment where you can build a story out of the things that have worked, but it is even more important to be in a place where it is ok when things are not going well too, and you can find means of support through these time(s)!
“When the confocal is not confocalling, a day with some struggles.” — Delan
In your medal award talk at the BSDB meeting, you mentioned your collaborative visit to the Netherlands was supported by a travelling fellowship from The Company of Biologists. Can you talk more about your experience of the visit?
In the interview for my PhD, a panellist said: “Congratulations on this step, but do not forget to get out of the lab.” I did not appreciate its significance till I had the chance to collaborate with the Hiiragi group in Utrecht, Netherlands. Indeed, as I mentioned, we were exploring the possibility of hydrostatic pressure’s role on neural crest cells. We needed to measure directly the change (if any) in Blastocoel’s hydrostatic pressure during gastrulation. During my stay, I had the privilege of meeting new people, where we discussed the struggles and triumphs we went through during our PhDs and the current limitations in our understanding of biological systems. Prof. Takashi Hiiragi and Dr. Moghe Prachiti’s expertise and advice throughout this collaboration were crucial for the successful outcome we achieved in this approach. This collaboration would not have been possible without the generous funds from The Company of Biologists. I highly recommend that, if you are reading this, you find your question, apply for funds, and explore beyond what is known – how exciting. Indeed, the science that we conduct at our benches builds our careers, but the science we do in collaboration builds scientific character.
What other project(s) did you work on during your PhD?
It is an exhilarating feeling to see your colleagues’ projects evolve and to have the chance to contribute with a suggestion, idea, or even a figure. I joined my colleague as a co-first author to investigate the role of RanBP1 on neural crest migration and its role in front-rear polarity. After neural crest induction (the focus of my main story), migration of these cells begins a widely studied phenomenon that has been previously linked to different signaling pathways (e.g., Wnt pathway). However, this work explored the possibility of a new player (RanBP1) in regulating this phenomenon by controlling cellular processes such as cell polarity.
Further, I have written a review of the most recent finding on the role of biomechanical cues on cell fate during early development. In this summary, we explore the latest in vitro, ex vivo, and in vivo studies on how mechanical cues interlink with biochemical signaling to promote tissue-specific fate and function of various cells. I found it is necessary to step out from my main work from time to time and come back with a refreshed mindset to tackle the next set of challenges.
If you took one abiding memory with you from your PhD, what would it be?
This is definitely a hard question to answer. There are so many different memories that led to this moment. Indeed, memories like surviving a global pandemic, walking in empty streets of central London, having the entire London tube for myself, the chance to go to the Netherlands, numerous conversations and mentorship from mentors and friends, and so many countless other memories. Simply, I cannot be dishonest to all of these career and character-building experiences by selecting just one!
What have you been working on since you completed your PhD? What’s next for you?
Neil deGrasse Tyson, world-renowned astrophysicist, said, “Ignorance is the natural state of mind for a research scientist … the boundary between what is known and unknown in the universe.” (Astrophysics for People in a Hurry; p32-33). In that boundary is where I aim to be. To this end, I joined the Acton Lab as a postdoctoral fellow, aiming to bridge the gap between our understanding of normal developmental processes and the transition into a pathogenic state. Generally, my interest remains the same: How do cells make their decisions? Can we influence that process for the betterment of our future?
What techniques or areas in developmental biology excite you the most lately?
Arguably, molecular biology spawned from developmental biology, and now we live in an era overwhelmed by the vast amount of information generated daily by this field. This invokes a paralyzing feeling of “Where do we go from here…?” Thus, I am not generally excited about particular techniques; however, I am quite interested in ideas. Indeed, I am very keen to see how developmental biology will piece together the intricate and detailed information we have of a certain cellular behavior to a much wider picture of understanding biological systems. “Chase ideas and not techniques, Delan!” was the second fundamental lesson I learned from Roberto Mayor during my first year as a PhD.
Outside of the lab, what do you like to do?
I did my PhD in London, so there is always something happening and to do! My general interests are photography, tennis, climbing, and swimming. However, my favourite remains a cup of joe and a conversation. So, If you are in town, let’s go for one?!
“When the Lab is not Labbing, a day to reset everything and go at it again!” — Delan
Alasaadi DN, Mayor R. Mechanically guided cell fate determination in early development. Cell Mol Life Sci. 2024 May 30;81(1):242. doi: 10.1007/s00018-024-05272-6. PMID: 38811420; PMCID: PMC11136904.
Alasaadi DN, Alvizi L, Hartmann J, Stillman N, Moghe P, Hiiragi T, Mayor R. Competence for neural crest induction is controlled by hydrostatic pressure through Yap. Nat Cell Biol. 2024 Apr;26(4):530-541. doi: 10.1038/s41556-024-01378-y. Epub 2024 Mar 18. PMID: 38499770; PMCID: PMC11021196.
Barriga EH, Alasaadi DN, Mencarelli C, Mayor R, Pichaud F. RanBP1 plays an essential role in directed migration of neural crest cells during development. Dev Biol. 2022 Dec;492:79-86. doi: 10.1016/j.ydbio.2022.09.010. Epub 2022 Oct 4. PMID: 36206829.
On the 8th-10th of May Disease Models and Mechanisms organised their first journal meeting entitled Preclinical Modelling of Human Disease and Therapy to showcase the latest advances in modelling human genetics diseases.
**Pics free to use**
The MRC National Mouse Genetics Network was a key organiser and participant with Owen Sansom (Director) and Pleasantine Mill (PI in the Congenital Anomalies Cluster) as members of the organising committee and many speakers and poster presenters to highlight the common thread that drives our scientific interests.
The meeting was also another chance to promote the Congenital Anomalies Variant of Uncertain Significance submission portal to the many national and international colleagues interested in human congenital diseases. Read our meeting report for further insights into a great programme and hugely stimulating three days.
This is part of the ‘Lab meeting’ series featuring developmental and stem cell biology labs around the world.
Where is the lab?
We are part of the Biomedical Research Institute, in the main campus of the National Autonomous University of Mexico in Mexico City (Instituto de Investigaciones Biomédicas, Ciudad Universitaria, Universidad Nacional Autónoma de México, UNAM).
Our aim is to integrate morphogenesis from a subcellular to a tissue-scale approach. We address this using the Drosophila respiratory system as model. This tissue forms complex morphologies that exploit basic cellular processes to build many types of tubes. In addition, these tubes interact with a range of tissues with different chemical and physical properties, making it a great system to compile sub- and supracellular mechanisms of development.
The Tissue Interactions Lab. From left to right: Pedro (astral projection), Samantha, Daniel, Berenice, Fernanda, Luis, and Rebeca (also astrally projected… we found it tough to gather everyone at the same time).
Lab roll call
Daniel: I’m the proud leader of this group.
Berenice: I recently joined this incredible lab. I’m academic technician and my participation has consisted of experimentally supporting the projects.
Luis: I’m a PhD student in the lab, part of the Biochemistry program of UNAM. I’m studying how different tissues can interact during embryogenesis to form different functional structures, from a mechanical point of view. As with all the lab members, I use the fruit fly as a model.
Fernanda: Undergraduate student (Biomedical Research), studying the role of protein secretion during tracheal development.
Pedro: In my BSc program in Biomedical Research we do one-year lab rotations. This is my first rotation and I’m studying apoptosis in the tracheal system.
Samantha: I am a Biology BSc graduate and I am currently applying to Master’s programs to officially join the lab. My research interests lie in studying the mechanisms that coordinate the development of the respiratory system with other tissues.
Rebeca: I am a Neuroscience BSc student interested in developmental biology.
Favourite technique, and why?
Daniel: Tough choice! We do a lot of live imaging in the lab and I really love watching, processing and analysing those movies. But I’m also fascinated by electron microscopy and the wonders you find in electron microcraphs.
Apart from your own research, what are you most excited about in developmental and stem cell biology?
Daniel: Non-model organism studies. The diversity of developmental processes in nature is truly fascinating.
How do you approach managing your group and all the different tasks required in your job?
Daniel: I think open communication with all lab members is key; also, an electronic calendar. We actually have a shared calendar where we schedule our meetings. the calendar includes deadlines, confocal bookings, things to buy, etc. So that we are all aware of what’s going on in the lab.
Are there any challenges unique to running a lab in Mexico?
Daniel: We have great talent, and funding from the University is good (at least for a fly lab). The main challenge is the speed of importing strains and reagents. We really have to plan ahead.
What is the best thing about where you work?
Daniel: Our campus is enormous! We have 10 bus lines just to get around. Besides that, our institute has hired many new faculty and we are building a great community among ourselves and with the rest of the labs here.
Berenice: Our campus is always open to the general public, it has a very active cultural life to which everyone has access. Particularly in our Institute, there are many activities that keep us together such as competitions in which the student community participates with different ideas, we all learn a lot, I love that!
Luis: This university has an infinity of opportunities to do whatever you want. Since it is the largest university in Latin America, it has a lot of cultural, sport and social activities to do. Just in our institute, here we have very diverse labs researching very different topics, and we have the opportunity of learning about other’s research with the different seminars organized every week.
Fernanda: The campus is considered a World Heritage site. It offers diverse activities and services to the entire community, including sports, scientific and cultural events, free language courses, etc. Plus, beautiful scenery can be enjoyed when traveling by bus or bike inside the campus. At the institute, our collaborative environment with experts from various fields promotes the development of exciting research projects.
Pedro: The whole campus is really nice; especially I like that it is surrounded by nature and grass to lie on.
Samantha: I haven’t had the opportunity to enjoy the entire campus yet, but from the times I’ve been there, I can say that it’s a big institution. This facilitates collaboration with other labs for mutual support, and the campus provides excellent resources to achieve research goals. Additionally, the university offers a free bus service to travel all around the campus.
Rebeca: I like that laboratories have diverse research lines because it allows us to learn about many scientific topics and participate in outreach events that enrich our research projects.
What’s there to do outside of the lab?
Daniel: Even though Mexico City is huge, I find everything I need just within my neighbourhood: A bouldering gym, good spaces for biking, and above all, amazing restaurants.
Berenice: Near the institute, we have the university cultural zone with a wide variety of entertainment at low-cost, even free: theater, cinema, concerts, museums.
Outside of our campus -located south of Mexico City- is Coyoacán, a space with a lot of history, and Xochimilco, full of traditions and with a lake that you can explore.
Luis: Mexico City is beautiful and it’s not a secret that its population is huge. Because of this you can find any activity or group of people that matches your interests. Personally, I love musical theater and this city has amazing local and international productions. Also, if you want to have fun at night, there are so many options of bars and clubs for everyone.
Fernanda: Mexico City is a place full of museums, theaters, parks, and restaurants. This means you can find all sorts of activities and delicious food to eat. Moreover, these places are open nearly every day and are easily accessible by subway.
Pedro: In general, I like spending my afternoons playing basketball on campus, but overall Mexico City is very diverse and you can find all kinds of activities.
Samantha: There are plenty of activities to enjoy around campus, such as visiting the botanical garden, exploring the museums, relaxing in the green spaces, or taking a long walk. These are just a few examples.
Rebeca: In the university, there are a variety of cultural spaces. You can attend art exhibitions, museums, theater plays, or concerts. Additionally, you can take art or dance classes. Personally, I enjoy learning languages, and the university offers that too. I’m currently learning Italian.
On 5 June 2024, Development’s Deputy Editor Steve Wilson (UCL) hosted a Development presents… webinar with three early-career researchers studying brain development. Catch up on the recordings of the talks.
Vertebrates, including humans, possess a “head” comprising cranial bones, the central nervous system, and sensory organs. It is believed that the emergence of the vertebrate “new head” is closely linked with the evolutionary acquisition of two cell populations: neural crest cells (NCCs) and cranial placode cells. Therefore, understanding the evolutionary origin and history of NCCs and cranial placode cells is crucial for understanding the evolution of vertebrates.
In vertebrate embryos, both NCCs and cranial placode cells arise from the border region between the neural plate and the epidermis. NCCs are unique because they produce not only cell types of ectodermal origin, such as sensory neurons and melanocytes, but also cell types of mesodermal origin, including smooth muscle cells, osteocytes, and chondrocytes.
Ascidians: fascinating model organisms for evolutionary developmental biology
Ascidians, commonly known as sea squirts, belong to the subphylum Urochordata or Tunicata, the sister group of vertebrates. They have been providing key insights into chordate developmental mechanisms and their evolution (FIGURE 1). Recent studies suggested that ascidian embryos have cells that share an evolutionary origin with vertebrate NCCs[1-3]. For example, ascidian cells called a9.49, located in the neural plate border, likely share an evolutionary origin with vertebrate NCCs[1]. Indeed, this cell pair expresses orthologous genes that specify the neural plate border cells and NCCs in vertebrate embryos. Furthermore, a9.49 cells can be reprogrammed to migratory pigment cells by overexpression of Twist, which encodes a transcription factor for mesenchyme specification. However, unlike vertebrate NCCs, ascidian NCC-like cells identified thus far do not produce cell types that are commonly of mesodermal origin. Therefore, it is believed that the multipotency of NCCs has been acquired within the vertebrate lineage after the split from the ascidian lineage.
FIGURE1 The sea squirt Ciona robusta (Ciona intestinalis type A)
A key observation made nearly 40 years ago
In 1987, Nishida found that ascidian cells called b8.17 and b8.19 give rise to muscle cells, nerve cord cells, and endodermal cells near the tip of the tail of embryos[4]. Both b8.17 cells and b8.19 cells are located in the neural plate border, which abuts the neural plate cells that give rise to the central nervous system. These cells express many orthologous genes that specify the neural plate border cells and NCCs in vertebrates. Therefore, if b8.17 and b8.19 cells share an evolutionary origin with vertebrate NCCs and produce cell types that are commonly ectodermal and mesodermal origin, the potential of NCCs to produce cells of multiple germ layers may date back to the last common ancestor (LCA) of vertebrates and ascidians, contrary to the prevailing hypothesis explained above.
In light of this context, we have decided to investigate the possibility that ascidian b8.17 and b8.19 cells share an evolutionary origin with vertebrate NCCs. First, we confirmed that b8.17 cells indeed produced muscle cells, as Nishida showed previously[4]. Second, we showed that these ascidian cells expressed Msx, Zic, Pax3/7, and Snai, which encode orthologs of key transcriptional factors specifying neural plate border cells of vertebrate embryos. We indeed showed that these genes were involved in specifying these ascidian cells. The location and the gene circuit for specification indicate that this ascidian cell population shares an evolutionary origin with vertebrate NCCs.
Do neural plate border cells of ascidian embryos share the evolutionary origin with vertebrate neuromesodermal progenitors (NMPs)?
In the middle gastrula stage, the ascidian neural plate border consists of four cells: b9.34, b9.33, b9.37, and b9.38, in order from posterior to anterior. In later embryos, the anterior two cells (b9.37 and b9.38) give rise to nerve cord cells (commonly of ectodermal origin), and the posterior two cells (b9.34 and b9.33) give rise to muscle cells (commonly of mesodermal origin) and other cells near the tip of the tail region[4]. On the basis of this observation, we hypothesized that these cells may share an evolutionary origin with vertebrate neuromesodermal progenitors (NMPs).
In vertebrates, Tbx6 is expressed in NMP-derived mesodermal cells and Tbx6 negatively regulates Sox2, which is expressed in NMP-derived spinal cord cells[5]. If our hypothesis is correct, the gene regulatory circuit consisting of Tbx6 (or its orthologs) and Sox2 (or its orthologs) will also be used for fate decisions in the neural plate border cells of ascidian embryos. Indeed, the anterior cells, which give rise to the nerve cord, expressed Sox2 ortholog (Sox1/2/3), and the posterior cells, which give rise to muscle, expressed Tbx6 ortholog (Tbx6-related) (FIGURE 2). Overexpression of Tbx6-related downregulated Sox1/2/3, and promoted muscle fate. Thus, the ascidian neural plate border cells and vertebrate NMPs share the gene regulatory circuit of Sox2 and Tbx6. In addition, a comparative single-cell transcriptome analysis also supported a close relationship between these ascidian cells and NMPs of zebrafish embryos.
FIGURE2 Gene expression pattern and fate decision of neural plate border of ascidian embryos
In this way, this ascidian cell population has properties of both vertebrate NMPs and NCCs. Therefore, the LCA of tunicates and vertebrates likely had cells with a hybrid property of NCCs and NMPs, and such ancestral cells may have produced both ectodermal and mesodermal cells.
Chordate origin of NCCs and NMPs
A logical follow-up question to ask is whether the Cephalochordata, the sister group of Olfactores, possessed NCC-like cells and NMP-like cells. Cephalochordates, commonly known as lancelets or amphioxus, are filter-feeding marine animals and are believed to retain ancestral features of chordates. Amphioxus is believed to lack cells homologous to vertebrate NCCs[6], although a recent preprint indicated that amphioxus possesses migratory NCC-like cells[7].
Interestingly, somites, notochord cells, dorsal neural tube, and hindgut of the posterior part of amphioxus embryos are produced from a cell population near the tip of the tail[8]. Therefore, amphioxus may possess NMP-like cells. Elucidating the developmental mechanism of this cell population should shed light on the evolution of the body plan of chordates.
A possible evolutionary history of the stemness of NCCs/NMPs
The ascidian NCCs/NMP-like cell population does not possess stemness: they do not show the ability of self-renewal, although they produce cell types that are commonly ectoderm and mesoderm origin. In vertebrates, the high stem cell-like potential of NCCs may depend on pluripotent factors or Yamanaka factors[9-12]. Among Yamanaka factor genes, only Sox1/2/3 was known to be expressed in the ascidian NCCs/NMP-like cells. This may be a reason why the ascidian cells do not have self-renewal ability.
Altogether, we propose a two-step model for the evolution of stemness of NCCs/NMPs: 1) the ability to produce ectodermal and mesodermal cells came first, and 2) the self-renewal ability, which led to acquisition of bona fide NCCs and NMPs. Future works on non-ascidian tunicates (e.g., Oikopleura), amphioxus, and cyclostomes will shed light on the evolution of the stemness of NCCs/NMPs. It would be particularly important to associate the evolution of the stemness of NCCs/NMPs with the evolutionary acquisition of pluripotent factor genes and whole genome duplications that occurred in the vertebrate lineages.
Rebecca K. Spangler, Guinevere E. Ashley, Kathrin Braun, Daniel Wruck, Andrea Ramos-Coronado, James Matthew Ragle, Vytautas Iesmantavicius, Daniel Hess, Carrie L. Partch, Helge Großhans, Jordan D. Ward
Ngoc Minh Phuong Nguyen, Eun Mi Chang, Maeva Chauvin, Natalie Sicher, Aki Kashiwagi, Nicholas Nagykery, Christina Chow, Phoebe May, Alana Mermin-Bunnel, Josephine Cleverdon, Thy Duong, Marie-Charlotte Meinsohn, Dadi Gao, Patricia K. Donahoe, David Pepin
Aicha El Ellam, Emily J. Alberto, Maria E. Mercau, Dimitrius T. Pramio, Krishna M. Bhat, William M Philbrick, Deborah Schechtman, Carla V. Rothlin, Sourav Ghosh
LS Ee, D Medina-Cano, CM Uyehara, C Schwarz, E Goetzler, E Salataj, A Polyzos, S Madhuranath, T Evans, AK Hadjantonakis, E Apostolou, T Vierbuchen, M Stadtfeld
Kristen Kurtzeborn, Vladislav Iaroshenko, Tomáš Zárybnický, Julia Koivula, Heidi Anttonen, Darren Brigdewater, Ramaswamy Krishnan, Ping Chen, Satu Kuure
Mekala Gunasekaran, Hannah R. Littel, Natalya M. Wells, Johnnie Turner, Gloriana Campos, Sree Venigalla, Elicia A. Estrella, Partha S. Ghosh, Audrey L. Daugherty, Seth A. Stafki, Louis M. Kunkel, A. Reghan Foley, Sandra Donkervoort, Carsten G. Bönnemann, Laura Toledo-Bravo de Laguna, Andres Nascimento, Daniel Natera-de Benito, Isabelle Draper, Christine C. Bruels, Christina A. Pacak, Peter B. Kang
Chiemela Ohanele, Jessica N. Peoples, Anja Karlstaedt, Joshua T. Geiger, Ashley D. Gayle, Nasab Ghazal, Fateemaa Sohani, Milton E. Brown, Michael E. Davis, George A. Porter Jr., Victor Faundez, Jennifer Q. Kwong
Nida Ozarslan, Corina Mong, John Ategeka, Lin Li, Sirirak Buarpung, Joshua F. Robinson, Jimmy Kizza, Abel Kakuru, Moses R. Kamya, Grant Dorsey, Phillip J. Rosenthal, Stephanie L. Gaw
Irina Lazar-Contes, Rodrigo G. Arzate-Mejia, Deepak K. Tanwar, Leonard C. Steg, Kerem Uzel, Olivier Ulrich Feudjio, Marion Crespo, Pierre-Luc Germain, Isabelle M. Mansuy
Luis Hernandez-Huertas, Ismael Moreno-Sanchez, Jesús Crespo-Cuadrado, Ana Vargas-Baco, Gabriel da Silva Pescador, José M. Santos-Pereira, Ariel A. Bazzini, Miguel A. Moreno-Mateos
Andrew S. Hagan, Scott Williams, Casey J. N. Mathison, Shanshan Yan, Bao Nguyen, Glenn C. Federe, Guray Kuzu, Joseph C. Siefert, Janice Hampton, Victor Chichkov, S. Whitney Barnes, Frederick J. King, Brandon Taylor, John R. Walker, Rui Zhao, Jimmy Elliott, Dean P. Phillips, Bin Fang, Rebekah S. Decker
Cristina Medina-Menéndez, Lingling Li, Paula Tirado-Melendro, Pilar Rodríguez-Martín, Elena Melgarejo-de la Peña, Mario Díaz-García, María Valdés-Bescós, Rafael López-Sansegundo, Aixa V. Morales
Elizabeth Elder, Anthony Lemieux, Lisa-Marie Legault, Maxime Caron, Virginie Bertrand-Lehouillier, Thomas Dupas, Noël Raynal, Guillaume Bourque, Daniel Sinnett, Nicolas Gévry, Serge McGraw
Archana Kamalakar, Brendan Tobin, Sundus Kaimari, M. Hope Robinson, Afra I. Toma, Timothy Cha, Samir Chihab, Irica Moriarity, Surabhi Gautam, Pallavi Bhattaram, Shelly Abramowicz, Hicham Drissi, Andrés J. García, Levi B. Wood, Steven L. Goudy
Justine Bajohr, Erica Y. Scott, Arman Olfat, Mehrshad Sadria, Kevin Lee, Maria Fahim, Hiba T. Taha, Daniela Lozano Casasbuenas, Ann Derham, Scott A. Yuzwa, Gary D. Bader, Maryam Faiz
Anna Kasprzyk-Pawelec, Mingjun Tan, Raneen Rahhal, Alec McIntosh, Harvey Fernandez, Rami Mosaoa, Lei Jiang, Gray W. Pearson, Eric Glasgow, Jerry Vockley, Christopher Albanese, Maria Laura Avantaggiati
Enric Bertran Garcia de Olalla, Gabriel Rodriguez-Maroto, Martina Cerise, Alice Vayssieres, Edouard Severing, Yaiza Lopez-Sampere, Kang Wang, Sabine Schaefer, Pau Formosa-Jordan, George Coupland
James Ronald, Sarah C.L. Lock, Will Claydon, Zihao Zhu, Kayla McCarthy, Elizabeth Pendlington, Ethan J. Redmond, Gina Y.W. Vong, Sanoj P. Stanislas, Seth J. Davis, Marcel Quint, Daphne Ezer
Isaia Vardanega, Jan Eric Maika, Edgar Demesa-Arevalo, Tianyu Lan, Gwendolyn K. Kirschner, Jafargholi Imani, Ivan F. Acosta, Katarzyna Makowska, Götz Hensel, Thilanka Ranaweera, Shin-Han Shiu, Thorsten Schnurbusch, Maria von Korff Schmising, Rüdiger Simon
Rasik Shiekh Bin Hamid, Fruzsina Nagy, Nikolett Kaszler, Ildikó Domonkos, Magdolna Gombos, Eszter Molnár, Aladár Pettkó-Szandtner, László Bögre, Attila Fehér, Zoltán Magyar
Abdull J. Massri, Alejandro Berrio, Anton Afanassiev, Laura Greenstreet, Krista Pipho, Maria Byrne, Geoffrey Schiebinger, David R. McClay, Gregory A. Wray
Daniel J. Stadtmauer, Silvia Basanta, Jamie D. Maziarz, Alison G. Cole, Gülay Dagdas, Gilbecca Rae Smith, Frank van Breukelen, Mihaela Pavličev, Günter P. Wagner
Haidee Tinning, Alysha Taylor, Dapeng Wang, Anna Pullinger, Georgios Oikonomou, Miguel A. Velazquez, Paul Thompson, Achim Treumann, Peter T. Ruane, Mary J O’Connell, Niamh Forde
Benjamin C. Klementz, Georg Brenneis, Isaac A. Hinne, Ethan M. Laumer, Sophie M. Neu, Grace M. Hareid, Guilherme Gainett, Emily V.W. Setton, Catalina Simian, David E. Vrech, Isabella Joyce, Austen A. Barnett, Nipam H. Patel, Mark S. Harvey, Alfredo V. Peretti, Monika Gulia-Nuss, Prashant P. Sharma
Amelia RI Lindsey, Jason M Tennessen, Michael A Gelaw, Megan W Jones, Audrey J Parish, Irene LG Newton, Travis Nemkov, Angelo D’Alessandro, Madhulika Rai, Nicole Stark
Mohammad Zeeshan, Ravish Rashpa, David J. Ferguson, George Mckeown, Raushan Nugmanova, Amit K. Subudhi, Raphael Beyeler, Sarah L. Pashley, Robert Markus, Declan Brady, Magali Roques, Andrew R. Bottrill, Andrew M. Fry, Arnab Pain, Sue Vaughan, Anthony A. Holder, Eelco C. Tromer, Mathieu Brochet, Rita Tewari
Valentina Gandin, Jun Kim, Liang-Zhong Yang, Yumin Lian, Takashi Kawase, Amy Hu, Konrad Rokicki, Greg Fleishman, Paul Tillberg, Alejandro Aguilera Castrejon, Carsen Stringer, Stephan Preibisch, Zhe J. Liu
Erik A. Ehlers, Kyle N. Klein, Margaret A. Fuqua, Julia R. Torvi, Javier Chávez, Lauren M. Kuo, Jacob McCarley, Jacqueline E. Smith, Gaea Turman, Danielle Yi, Ruwanthi N. Gunawardane, Brock Roberts
Barbara Varnum-Finney, Adam M. Heck, Sanjay R. Srivatsan, Stacey Dozono, Rachel Wellington, Cynthia Nourigat-McKay, Tessa Dignum, Cole Trapnell, Brandon Hadland
In this SciArt profile, we meet Gabriela Krejčová, a postdoctoral researcher at the University of South Bohemia, Czech Republic, who enjoys making nature-inspired jewellery.
Forest-inspired pendants and earrings with real mushrooms, ferns and lichens.
Can you tell us about your background and what you work on now?
My first scientific endeavour was carried out in the field of cancer immunotherapy. I found the metabolic changes of tumour cells particularly remarkable at the time. After completing my undergraduate studies, I started looking for a new laboratory where I could conduct my master’s thesis. I came across Dr. Adam Bajgar, who at the time was working on the metabolic polarization of Drosophila melanogaster immune cells during bacterial infection. Since it is well established that the metabolic setting of pro-inflammatory macrophages resembles in many aspects the metabolic changes occurring in some types of cancer cells, I changed my field of study because this topic represented a nice link to my previous research focus. During my PhD studies, I began to look into the signalling molecules released by the immune cells in response to their metabolic polarization, which subsequently mediate the inter-organ communication. I also become fascinated by the functional versatility of macrophages and their regulatory role in various stress conditions, which is my current focus.
A collection of pendants with real ferns.
Were you always going to be a scientist?
I would say I’ve always enjoyed unravelling the unknown, whether it was the mysteries of nature or Egyptian hieroglyphs. I remember wishing for a little spooky laboratory, and I cherish the memories of getting my own small kid’s microscope and exploring the world up close. Oddly enough, my dream job as a child was actually a fashion designer, which reflected my love for art.
Spring-inspired watercolor painting of Verpa bohemica mushroom, lily of the valley (Convallaria majalis), Hepatica nobilis and Easter eggs.
And what about art – have you always enjoyed it?
By all means! I’ve always enjoyed all kinds of crafts and I’ve always had a desire to create pretty things – from drawings and paintings to jewellery and decorations such as traditional Easter eggs decorated with wax. Another passion of mine has always been dancing, so I found another way to express my urge for creating in designing and decorating dance costumes.
A set of earrings and a pendant with false chanterelle mushrooms (Hygrophoropsis aurantiaca), pink chervil, violet beautyberry, fern and lichens.
How do you make your jewellery?
I make my jewellery exclusively from products of nature and clear epoxy resin. So first, I forage for all sorts of flowers, mushrooms, lichens, mosses, ferns or berries to create tiny microworld compositions. Before casting, which is usually a multi-step process, all materials must be dried in a special way to retain their original colours and shapes. After demoulding, all must be sanded and polished, which is the most time-consuming part. Then I attach the jewellery findings and the piece is finally finished. The whole process takes approximately two weeks.
Sphere-shaped pieces are the most time consuming type of pendants I create.
What or who are your most important artistic influences?
My biggest muse is definitely nature itself. My goal is to preserve the beauty and diversity of shapes, structures, patterns and colours that nature has already created, and perhaps just slightly transform these pieces into small compositions and make them wearable. In this way, I would like to give people a piece of unspoiled nature that they can keep constantly with them.
I create also taxidermy jewellery with real beetles that I buy already preserved at insect sales exhibition.
Does your science influence your art at all, or are they separate worlds?
I would say it’s rather the opposite – my art influences my scientific outputs, or at least I hope so. I firmly believe that scientific imaging techniques provide ample room for artistic expression, and I hope that this is sometimes reflected in my scientific output. I especially enjoy the visualization of macrophages by confocal and electron microscopy, and the beauty of immune cells brought me much joy during my PhD studies.
Journal Covers for Development and The EMBO Journal.
What are you thinking of working on next?
It is now spring season in the Czech Republic, so everything is thriving and blooming. For me, it is the time of year when I need to stock up for the upcoming year so I have enough material to make jewellery in the colder months. Therefore, I have a lot of collecting, foraging and mushrooming ahead of me, which means a lot of quiet and fulfilling time spent in nature.
Pendants with many types of colourful lichens and fern
On the topic of mechanics and morphogenesis chaired by Development Editor, James Wells (Cincinnati Children’s Hospital Medical Center)
Wednesday 19 June – 15:00 BST
Clémentine Villeneuve (Max Planck Institute for Molecular Biomedicine) ‘Tissue-scale mechanics control stem cell fate and positioning during epithelial development’
Louis Prahl (University of Pennsylvania) ‘Branching, crowding, and packing: engineering the developing kidney epithelium’
Kyojiro Ikeda (University of Vienna) ‘Nanometric 3D printing: sculpting bristles by dynamic microvilli’
At the speakers’ discretion, the webinar will be recorded for viewing on demand. To see the other webinars scheduled in our series, and to catch up on previous talks, please visit: thenode.biologists.com/devpres
Neurofly2024 is the main conference on neurobiology of Drosophila, taking place every 2 years, and has been rotating across Europe for the last 40 years. The Company of Biologists Travel Bursaries will cover the registration fees of PhD students, enabling a wider participation in the Neurofly.
We have now advertised the bursaries, please visit:
The 20th Biennial European Drosophila Research Conference (Neurofly) will take place from 2 to 6 September 2024 at the beautiful University of Birmingham campus, in UK.
Neurofly 2024 will allow the opportunity for researchers from across the globe to meet to discuss their latest research and observations principally on the neurobiology of Drosophila but also including studies using other invertebrate model organisms. Drosophila offers major advantages for neurobiological research due to the wealth of genetic tools to observe and manipulate the nervous system. We aim to provide a venue for wide-ranging discussions and interactions between junior and senior researchers in an inclusive interdisciplinary environment that will allow the exchange of results, ideas and new concepts. A wide range of sessions will include Developmental and cellular neuroscience, Brain homeostasis and metabolism, Brain disease, injury and ageing, Gene expression and molecular neuroscience, Neural circuits and behaviour, Plasticity and remodelling.
We have lined up eight wonderful plenary speakers and the rest of talks will be selected from abstract submissions, allowing exciting, emerging research to be presented by early career and established researchers. We will also have a practical demo workshop on bridging connectomics and transcriptomics. And fun activities, including a trip to Stratford and the gala conference dinner.
Registration early bird and abstract submission deadline is 16 June 2024.
Please be aware that lecture theatre capacity is limited: please register with time to avoid disappointments.
A recent paper “Neural crest origin of sympathetic neurons at the dawn of vertebrates” challenges the prevailing dogma that the sympathetic ganglia arose only in jawed vertebrates. Instead, based on the findings in the sea lamprey, the authors suggest a late-developing rudimentary sympathetic nervous system may be present in the earliest jawless vertebrates. First author Brittany Edens and corresponding author Marianne Bronner tell us the story behind the paper.
Wild-caught mature ammocete sourced from the Great Lakes.
How did the project start?
Marianne: Brittany was doing some staining of lamprey larvae with different antibody markers with the goal of defining different types of neurons in the developing enteric nervous system. We got together to look over the data and realized that some of the neuronal staining was not in the gut but dorsal to the gut in a position that was appropriate for the sympathetic nervous system. This was a surprise since lamprey are not supposed to have a sympathetic nervous system. So we started looking for more markers to test this possibility more rigorously.
Detection of sympathoblasts in late embryonic lamprey: The catecholamine biosynthetic processing enzyme tyrosine hydroxylase (TH) is detected by immunohistochemistry at T27 in (a) transverse sections and (b) lateral whole-mount. TH+ sympathoblasts are localized dorsal to the yolk tube and flank the midline in bilateral streams. Scale bars=50mm (a) and 10mm (b).
Why do you think it’s been previously thought that jawless vertebrates lacked the sympathetic nervous system?
Marianne: That’s easy to answer. We think people (including ourselves) were initially looking at the wrong time. In higher vertebrates, the sympathetic nervous system develops rather early in development, initiating when neural crest cells begin to coalesce around the dorsal aorta. We actually looked at comparable stages in lamprey and did not see the markers characteristic of sympathetic neurons co-expressed. However, when we looked at larvae at about 1 month of development, we observed not only sympathetic marker genes but also the transcription factors known to be involved in their specification. Thus, there was a heterochrony in terms of the time of differentiation.
Why did you choose the lamprey to answer your questions?
Marianne: Lamprey are jawless vertebrates and have an important phylogenetic position at the base of the vertebrate tree of life. Lamprey fossils from the Cambrian period resemble modern lamprey in morphology. While we have no access to a “vertebrate ancestor” and lamprey have continued to evolve, they still are the closest approximation to what we think the ancestor may have looked liked.
Can you summarise the key findings of the paper in a paragraph?
Marianne: In gnathostomes (jawed vertebrates), the neural crest gives rise to a fate-restricted sympathoadrenal progenitor from which sympathetic neurons of the autonomic nervous system arise. A transcriptional program including Ascl1, Phox2b, and Hand2 specifies neural crest towards sympathoadrenal fates, and also promotes catecholaminergic identity (i.e., expression of tyrosine hydroxylase and dopamine beta-hydroxylase enzymes). Upon maturation, these neural crest-derived sympathetic neurons will express various pan-neuronal genes, as well as genes specific for catecholaminergic function. While the earliest vertebrates, which lacked jaws, were historically believed to lack sympathetic neurons within the trunk, we found evidence of these cells in the jawless vertebrate sea lamprey. We found that the same core transcription factors involved in sympathoadrenal specification were co-expressed in cells throughout the trunk in lamprey, as were the catecholamine pathway enzymes. Later in larval stages, these cells upregulated expression of pan-neuronal markers. Lineage tracing indicated a conserved origin in the trunk neural crest and finally, RNA-sequencing analysis suggested a transcriptional profile that was consistent with sympathetic neuron identity. Altogether our findings challenge the prevailing dogma that the sympathetic ganglia are a gnathostome innovation.
Were you surprised to find a rudimentary sympathetic nervous system in the lamprey?
Marianne: Yes indeed. We expected to see no sympathetic nervous system since that is what the literature says. It was a real surprise to see neurons in the right place with characteristics of sympathetic neurons.
How does the lamprey’s sympathetic nervous system differ from that in jawed vertebrates?
Marianne: There are many fewer neurons than seen in amniote embryos and no distinct ganglia. Just a few scattered cells all along the trunk region.
Ongoing proliferation of sympathoblasts in lamprey ammocetes: (a-c) HCR detection of Th (teal) and EdU staining (red) in ammocetes following an 8 hour EdU incubation. EdU detection in Th-expressing cells (indicated by arrowhead) reveals active division of sympathetic progenitors/neurons in lamprey trunk into ammocete stages. (d-g) Immunohistochemical detection of TH (teal) and EdU (red) co-expression in transverse sections of ammocetes following an 8 hour EdU incubation. Co-expression is denoted by arrowheads (n-p). DAPI is shown in white. Scale bars=50mm.
Brittany, were there any particular result or eureka moment that has stuck with you?
Brittany: Most of the experiments were performed on late-stage embryos and ammocetes that weren’t much larger, and as a result, a lot of our analyses documented sympathetic progenitors and immature neurons. To get a more mature population of sympathetic neurons for the final sequencing experiment, we actually had to source much larger, older ammocetes directly from the Great Lakes off-season. When they arrived at the lab, I was a bit shocked. They were so much larger than anything I was accustomed to working with, and I wasn’t sure if my tools were even appropriate for the dissections. The long and the short of it: the dissections were fine, but more importantly, the sympathetic trunks of these later-staged ammocetes were visibly discernible under the dissecting microscope. Of course we trusted our data from the late-stage embryos and the younger ammocetes, but I think it’s true that seeing is believing.
And the flipside: any moments of frustration or despair?
Brittany: When it comes to experiments and data, I try to keep a level head and clear perspective. As scientists, we are after the truth, and every clear result (even the ones we didn’t want or expect) gets us closer to the truth. The scientific process really does work, and having trust in that goes a long way on more challenging days.
What’s next for you, Brittany?
Brittany: Ultimately, I would like to be an independent investigator. I’m drawn to comparative embryology as a means to understand how peripheral sensory and autonomic neural systems first arose in vertebrates, and how genetic and environmental changes have driven diversification and adaptation of these systems over time. That’s a bit longer term, since I’ve just crossed the three-year mark as a postdoc, but in the meantime we have a collaboration with the Cai Lab at Caltech that I’ve been very excited about. We are looking to leverage their spatial barcoding technology, seqFISH, to better understand neuronal heterogeneity within the peripheral nervous system. Another endeavor I would like to mention is the work I’ve been doing with the support of the Caltech CTLO (Center for Teaching, Learning, and Outreach). One of my goals is to make hands-on science education more accessible to younger students, and with support from the CTLO and feedback from our local high school students, I have been developing grade-appropriate protocols and resources to introduce topics in embryology and neurobiology.
And Marianne, where will this story take the lab?
Marianne: We are continuing to work on many different neural crest derivatives in lamprey and would like to understand whether the gene regulatory circuits resulting in neural crest differentiation into things like peripheral neurons, craniofacial structures, etc. are conserved to the base of vertebrates. Right now, we are particularly interested in the enteric nervous system and how it has become elaborated.
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