Here are the highlights from the current issue of Development:

Computing branching pattern complexity

Bile – a fluid that aids digestion – is transported from the liver to the intestine through the bile duct. Bile reaches the bile duct itself via a complex, highly branched structure called the intrahepatic biliary network. This network spreads throughout the liver but how it is patterned is unclear. On p. 2595, Takuya Sakaguchi and colleagues report a novel computational approach to analyse the 3D structure of this network in developing zebrafish. They use a computational algorithm that renders confocal scans of labelled livers into compact representations of the intrahepatic biliary network, which recapitulate endogenous branching patterns and simplify the branched networks into segments amenable to further analysis. Using this computational approach, the authors identify a small molecule inhibitor of Cdk5 that reduces the density of the biliary network, leaving liver size and biliary epithelial cell numbers unchanged. They also experimentally manipulate the downstream Cdk5-Pak1-LimK-Cofilin cascade to increase branching density, and demonstrate a role for this cascade in regulating actin dynamics in biliary epithelial cells. These findings demonstrate the utility of this computational approach to studying branched tissues and highlight the Cdk5-Pak1-LimK-Cofilin cascade as a potential therapeutic target for liver disorders.

No lung development without Sin(3a)

Sin3a is a co-repressor that modulates the transcription of numerous genes by complexing with chromatin remodelling enzymes that modify histones. Here, Barry Stripp and co-workers reveal a key role for Sin3a during lung development in mice (p. 2618). They report that the foregut endoderm-specific deletion of Sin3a leads to failed lung development and the death of neonatal pups due to respiratory failure. Although lung buds form in early mutant embryos, subsequent branching morphogenesis and development fails, with loss of both the lung endoderm and lung epithelium. Loss of Sin3a also disrupts lung mesoderm differentiation, possibly due to aberrant epithelial-mesenchymal interactions. Interestingly, histone H3 acetylation levels show no significant change in Sin3a-deficient epithelial cells, indicating that loss of histone deacetylation activity is unlikely to contribute to the lung phenotype. Instead, lung epithelial progenitor cells in mutant embryos enter a senescence-like state and arrest in G1. This cell cycle arrest is partially mediated by upregulation of the cell cycle inhibitors Cdkn1a and Cdkn2c. Together, these findings reveal that Sin3a plays a crucial role in regulating early lung endoderm progenitor cell fate, via the transcriptional repression of cell cycle inhibitors, to prevent the induction of a senescence-like state. Whether Sin3a plays a similar role in the postnatal lung awaits further investigation.

Set(d1b)ing oocyte gene expression

Mouse primordial germ cells (PGCs) – the precursors of oocytes and sperm – undergo extensive DNA demethylation as they migrate to the genital ridge. In primary oocytes, DNA undergoes re-methylation, and lysine residues on the tails of histone H3 become methylated. This important epigenetic mark is created in mammals by H3K4 methyltransferases, including Setd1a and Setd1b. Setd1a plays no role in oogenesis, but now Andrea Kranz and colleagues report that the loss of Setd1b in mouse oocytes causes female sterility (p. 2606). Although metaphase II-stage oocytes develop in female Setd1bconditional mutants, both their zona pellucida and meiotic spindle are abnormal. Upon fertilisation, extra sperm enters the perivitelline space of the mutant oocytes and the zygotes become stuck at the pronuclear stage. RNA profiling reveals that Setd1b is required for the expression of key oocyte transcription factors and that its inactivation causes twice as many mRNAs to be upregulated as downregulated. Thus, Setd1b likely promotes the expression of transcriptional repressors, possibly Zfp-KRAB factors, which maintain the oocyte-specific expression programme in late development by reducing earlier, unwanted gene expression. These findings reveal a novel role for Setd1b in regulating the oocyte-to-embryo transition, possibly by regulating the late-oocyte gene expression programme.

PLUS…

The status of the human embryo in various religions

Research into human development involves the use of human embryos and their derivative cells and tissues. How religions view the human embryo depends on beliefs about ensoulment and the inception of personhood, and science can neither prove nor refute the teaching of those religions that consider the zygote to be a human person with an immortal soul. In his Spotlight article, William Neaves  discusses some of the dominant themes that have emerged with regard to how different religions view the human embryo, with a focus on the Christian faith as well as Buddhist, Hindu, Jewish and Islamic perspectives.

Interspecies chimeras for human stem cell research

Interspecies chimeric assays are a valuable tool for investigating the potential of human stem and progenitor cells, as well as their differentiated progeny. In their Spotlight article, Hideki Masaki and Hiromitsu Nakauchi discuss the different factors that affect interspecies chimera generation, such as evolutionary distance, developmental timing, and apoptosis of the transplanted cells, and suggests some possible strategies to address them.

A framework for understanding the roles of miRNAs in animal development

MicroRNAs (miRNAs) contribute to the progressive changes in gene expression that occur during development.  In their Review, Chiara Alberti and Luisa Cochella present a view of miRNAs as a hierarchical and canalized series of gene regulatory networks. In this scheme, only a fraction of embryonic miRNAs act at the top of this hierarchy, with their loss resulting in broad developmental defects, whereas most other miRNAs are expressed with high cellular specificity and play roles at the periphery of development, affecting the features of specialized cells.

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The Walentek lab studies the molecular mechanisms of mucociliary development, regeneration and disease. Mucociliary epithelia line the embryonic epidermis as well as the respiratory tract of many animal species, and provide an important first line of defense against pathogens for the organism. We are particularly interested to elucidate the interactions between cell signaling, transcriptional and post-transcriptional regulation of gene regulatory networks, and the morphogenetic processes at the cellular and tissue-wide levels, which facilitate complex tissue formation and function. Our work aims to provide crucial insights into the logic of self-organization in biological systems as well as into the molecular mechanisms underlying chronic lung diseases.

Two PhD positions will be available starting October 2017 (or later). The group is supported through the Emmy-Noether-Program by the DFG, which provides fully funded PhD positions (65%). We offer a great environment to perform cutting-edge science at the interface between basic biology and translational medical studies. The Walentek lab is affiliated with the excellent Freiburg Medical Center (Universitätsklinikum Freiburg) and situated in the multidisciplinary research building of the ZBSA (Center for Biological Systems Analysis). This setting provides access to state-of-the-art core facilities and collaborations, including advanced light and electron microscopy, proteomics, computational biology, mathematical modeling and genetics/ genomics. PhD students will have the option to participate in the Spemann Graduate School of Biology and Medicine and benefit from advanced training and mentoring opportunities.

Prior experience in cell/developmental biology, genetics/ genomics, or (bio)informatics is highly desired. Interested students should apply with a cover letter stating their motivation, a CV (incl. list of publications if applicable), and contact information for two scientific references to applications_walenteklab@gmx.de .

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Antibodies are one of the most commonly used research reagents. However, due to their innate variability, finding the right antibody can be a challenge. Scientists devote a significant amount of time sifting through the literature to find antibodies that have been shown to work under specific experimental contexts matching their research interests. This process often takes several hours, sometimes even days, wasting valuable time that could otherwise be used more efficiently.

BenchSci has created a solution to this problem by developing a machine-learning algorithm that decodes primary research papers to identify the antibody used and the associated experimental contexts in each paper. Scientists can search their protein of interest on BenchSci’s open-access online platform, and find results displayed in the form of individual figures from scientific papers in which antibodies against that protein were used. These figures are easily filterable to allow users to narrow down their search results to the antibody use cases that best fit their experimental contexts and, ultimately, find the best antibodies for their experiments.

On the open-access BenchSci platform, we have developed several features that can facilitate evidence-based antibody selection. Check them out below!

1. Search results can be viewed as “Figures” or “Products” list

Depending on your preference, you may wish to examine figures first then identify the antibody used, or you may wish to examine antibodies first then view associated figures that supported its use.

2. Figures and Products can be filtered by specific experimental contexts

Using filters such as Techniques, Tissue, and Cell Lines, and more, you can easily identify published figures and the antibody used that match your experimental interest in seconds.

3. Direct link to original paper and antibody supplier

If you found a figure or product of interest, you can directly link to the original paper or the supplier website, respectively.

4. Save Figures and/or Products to “My Bench”

For individual figures or products of your interest, you can track them by saving to folders in “My Bench”.

Within My Bench, you can organize the figures and products into different project folders.

5. Submit Reviews for your (least) favourite antibody

Data that proves an antibody didn’t work under certain contexts is equally important as data that showed the antibody worked. Unfortunately, this information is not captured anywhere else other than in your lab notebook.

The Review function is where you can let fellow scientists know that you have tested a certain antibody, and whether or not it worked as intended.

6. Sharing the knowledge

You can email individual figures or products to your colleagues, labs members, or collaborators with the click of a button.

We would like to invite you to create a free academic account at www.BenchSci.com, and experience how efficient evidence-based antibody selection can be!

For any questions, suggestions, or comments, please get in touch with Maurice (maurice@benchsci.com). We would love to hear from you.

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In the very earliest stages of life, mammalian cells multiply and form the embryo. New research from the University of Copenhagen suggests that this process might be much simpler than we thought. The development of the embryo can be cut down to the cell’s ability to count their neighboring cells.

The article ‘Four simple rules that are sufficient to generate the mammalian blastocyst’ is a product of StemPhys, a new multi-disciplinary initiative between The Faculty of Health and Medical Sciences, University of Copenhagen and the Niels Bohr Institute funded by the Danish National Research Foundation. The work is published in the journal PLoS Biology.

See more here: http://danstem.ku.dk/news/the-earliest-stages-of-life-might-be-simpler-than-we-thought/

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Worm art at #Worm17

Each year at the International C. elegans Conference Ahna Skop organises a Worm Art Show with winners selected by the meeting participants (find out more about the history of the show here). 

2017’s winners have just been announced – read about them over at the GSA’s Genes to Genomes blog (a great site for your bookmarks if you haven’t visited it already!).

The Best in Show this year was won by Beata Mierzwa’s Bond-themed image (Beata told us all about her awesome art last year)

FASEB BioART Scientific Image & Video Competition

Each year FASEB runs a BioArt competition to “share the beauty and breadth of biological research with the public”, and their 2017 competition is now open with a submission deadline of August 31, 2017. Entries can be submitted to four categories:

• Fluorescence or Electron Microscopy
• All Other Life Science Images
• Video
• NEW! 3D Printing

As last year’s winners show, developmental biology images are well appreciated!

This highly-detailed image of the central nervous system from a horned dung beetle (Onthophagus sagittarius) was captured with a laser-scanning confocal microscope. Imaged during the late pupa stage, this beetle was about to complete metamorphosis. The optic lobes (top) are in the process of growing and extending towards the outer surface of the head to form a pair of compound eyes. Different colored fluorescent labels were used to visualize the distribution of a structural protein (red), the neurotransmitter serotonin (green), and genetic material (blue). This image is from a National Science Foundation-supported research project on the evolution of novel and complex traits. By Eduardo Zattara, Armin Moczek, Jim Powers, Jonathan Cherry, and Matthew Curtis

o form new tissues and structures during development, populations of cells move, often over long distances. This movement, called cell migration, is highly coordinated across space and time. This zebrafish (Danio rerio) larva was labeled with red fluorescent molecules to identify the migrating cells that will compose the surface of the fish’s skin, or epithelium. Genetic material (blue) and, in a subset of cells, a structural protein (green) were also labeled. Although this image is of a fixed zebrafish, the research group is using live imaging to observe the movement of these cell populations in real time. Drs. Ruiz and Eisenhoffer are researching cell migration to better understand normal facial development as well as the genetic mutations in humans that lead to congenital birth defects such as cleft lip and palate. By Oscar Ruiz and George Eisenhoffer

Spinal cord injuries often lead to lifelong disabilities. To achieve functional recovery, the nerve pathways that were damaged must be reconnected. One potential solution is to induce the nerve stem cells already present in the adult spinal cord to reestablish these connections. This requires activating the stem cells to grow long extensions while simultaneously preventing the formation of scar tissue, which can block these extensions. This image from a NIH National Institute of Biomedical Imaging and Bioengineering-supported study shows a mouse nerve cell (blue/green) on a synthetic nanofiber gel (purple) designed to mimic healthy spinal cord tissue. The nerve cell has grown long extensions (green) into the gel. The researchers found that injecting these nanofibers at the site of a spinal cord injury reduced scar formation and helped to restore hind leg function in mice. By Mark McClendon, Zaida Alvarez Pinto, and Samuel I. Stupp

Proper bone and cartilage development is critical to support body structure and protect vital organs. For example, the skull supports and protects the brain while the ribs protect the heart, lungs, liver, and spleen. As seen in this image of mice at different developmental stages, bone (green) and cartilage (reddish-orange) formation begins during the embryonic period (far left) and continues throughout adolescence (far right). The NIH National Institute of Dental and Craniofacial Research supports this research program on genetic mutations that cause abnormal skeletal formation and underlie many congenital birth defects. By William Munoz, Karla Terrazas, and Paul Trainor

C-shaped rings of cartilage (red) give the trachea, or windpipe, its shape and strength. Because all oxygen that reaches the lungs must first pass through the trachea, its structural integrity is essential to human life. In conditions like tracheomalacia, malformation of the cartilage weakens the trachea, leading to airway collapse. The NIH National Heart, Lung and Blood Institute supports this research project on identifying the signals that prompt developing cartilage to segment into C-shaped rings. This image from a mouse is helping the investigators examine the organization of nerve cells (green) and their potential role in directing cartilage (red) formation. By Randee Young and Xin Sun

Olympus Image of the Year

Olympus has announced its first Image of the Year competition for life sciences:

“Show us and the world the art of light microscopy and illustrate the details of life with your most beautiful image.”

Deadline for entries is 31st October

Royal Society Photography Competition

This competition is “open to scientists, and winning entries are chosen according to 2 key criteria: they should be aesthetically pleasing, and convey an interesting scientific phenomenon.” Deadline is 31st August, more details here.

Among the categories, ‘Micro-imaging’ is probably the best bet for developmental biologists! Here’s a couple of runners up of last year’s competition:

Runner up: Micro-imaging. “The spiralled snake axis” by Tyler Square. During early growth and development, most vertebrate animals look quite similar. Here, in this image of a one-day post-oviposition African house snake (Boaedon fuliginosus), we see many features that tie all vertebrates together: pharyngeal arches surrounding the mouth and throat (with gill slits between them), muscle segments (called somites) which will eventually contribute to the spine and musculature, and a chambered heart connected to a closed circulatory system to move oxygen and nutrients to tissues. During and after these stages, the novelties specific to a species or lineage begin to develop – here the 5mm long elongated body of the snake develops as a spiral to fit inside the egg.

Runner up: Evolutionary Biology. “Polychaetous worm with engine and wagons” by Fredrik Pleijel. This trainworm (Myrianida pinnigera), which is 35mm from head to tail, lives on the sea floor. Its front end, the trainworm’s engine, is followed by a row of carriages called ‘stolons’ that increase in size towards the worm’s tail end. The carriages are the worm’s swimming sexual organs. When the trainworm is mature, the last carriage in the train lets go and detaches. It swims up the water column to reproduce. The carriages, unlike the engine, all lack a gut and are full of either sperm or eggs. In the water column the well-developed sensory organs seek out another stolon to mate with. After mating the male stolons die. The females survive a short time to shelter the embryos, which are carried in their bellies. Meanwhile, the trainworm on the sea floor continues to produce stolon carriages.

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21th “Evolutionary Biology Meeting at Marseilles”, sept 26-29 2017

Pre-program at: http://aeeb.fr/?page_id=947

Registration & abstract submission is still an option

All information at: http://aeeb.fr/?page_id=524

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A Postdoctoral position is available in the laboratory led by Ricardo Mallarino, Department of Molecular Biology, Princeton University (www.mallarinolab.org). The lab focuses on uncovering the genetic and developmental mechanisms by which form and structure are generated during vertebrate embryogenesis. We combine the study of emerging and traditional model organisms to explore questions relating to patterning and evolution of novelty in the mammalian skin. The lab uses a variety of approaches, including experimental embryology, genetics, genomics, imaging, and mathematical modelling to uncover gene function and understand mechanisms of evolutionary change.

The lab is currently focusing on two model systems: striped rodents and gliding mammals. Available projects include:

• Spatial control of genes implementing stripe patterns
• Molecular mechanisms of stripe pattern specification
• Comparative genomics and evolution of pigment patterns
• Molecular mechanisms of gliding membrane formation and evolutionary genomics of gliding

While the position entails working on one of these areas, the candidate is expected/encouraged to take a leading role in the conceptual and experimental design of the project. In addition, there will be significant opportunities for pursuing original ideas that fall within the general focus of the lab.

Applicants with a strong background in developmental biology, genetics/genomics, and/or molecular/cell biology are encouraged to apply. A Ph.D. in these disciplines is preferred, however candidates holding a Ph.D. in other areas that have strong laboratory and/or bioinformatics skills will also be considered. Prior experience with experimental embryology, cell/tissue culture, and microscopy would be very beneficial. However, necessary training will be provided for a motivated candidate. Excellent oral and written communication skills and the ability to work independently or in collaboration are essential.

To apply for this position please submit a CV, a cover letter describing research interests, and contact information for three references who can comment on your research to rmallarino(at)princeton.edu. Applications will be reviewed promptly until the position is filled. Princeton University is an equal opportunity employer and complies with applicable EEO and affirmative action regulations.

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Postdoctoral Fellowship at UCSF.
An NIH funded postdoctoral fellow position is immediately available in the Knox Lab at the University of California, San Francisco (http://profiles.ucsf.edu/sarah.knox).
The Knox Lab aims to define fundamental mechanisms underlying the development, regeneration and aging of exocrine organs including salivary and lacrimal glands and the pancreas. In addition to our staple tools of mouse genetics, fetal organ culture and 3D imaging, we utilize a number of cutting edge approaches including organoids, live cell imaging, epigenetic assays (ATAC-seq) and single cell sequencing. The candidate will utilize these tools to discover how exocrine organs develop, regenerate and age in response to cues from the autonomic and sensory nervous systems.
Desired skills and experience
Our lab is looking for highly motivated candidates with a recent PhD and a record of productive research as evidenced by at least 1 published manuscript in a peer reviewed international journal.
Candidates with previous experience in molecular biology, organogenesis, epigenetics, and/or mouse models are preferred.
Excellent written and oral communication skills in English and the ability to work independently and as part of a collaborative team are a precondition.
Please submit your cover letter, CV/resume including list of publications and names and contact information for 3 references to: sarah.knox@ucsf.edu

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Here we highlight some developmental biology related content from other journals published by The Company of Biologists.

Jacky Goetz, who works on intravital imaging methods and biomechanical forces during tumour development, was featured as a Cell Scientist to Watch

David Bryant and Aaron Johnson reported from The Company of Biologists’ workshop ‘Intercellular interactions in context: towards a mechanistic understanding of cells in organs’ 

George, et al. find that amphiregulin is not required for reprogramming non-mammary stem cells to a mammary cell fate

Fišerová, et al.  combine super-resolution microscopy with robust image analyses to discern the organization of chromatin at nuclear pore complexes

Lange, et al. show that phosphatase PP2A is dysfunctional in t^w18 mutant mice, and essential for Nodal and WNT signaling in the epiblast.

Tomankova, et al. describe how embryonic epidermis development is influenced by nitric oxide, where it has been linked to the development of ionocytes, multi-ciliated cells and small secretory cells.

Campla, et al. show that loss of Pias3 in mice results in altered dorso-ventral patterning of retinal cone photoreceptors by modulating the expression of a subset of genes, but does not affect rod development.

Villiard, et al.  report the presence of senescent cells in several transient structures in developing amphibian and teleost fish, suggesting novel mechanisms of morphogenesis that appeared early in vertebrate evolution

Strassman, et al. report the first targeting of an invertible gene trap to generate a conditional Prdm16 mouse allele and its use to assess phenotypic consequences of Prdm16 loss during craniofacial and brain development.

Goyal, et al. combine microfluidics, live imaging and systems biology to develop a new approach for the functional analysis of sequence variants in the highly conserved Ras signaling pathway

An interview with Bauer Fellow and L’Oréal Women in Science Laureate Lauren O’Connell talks about her research, outreach and the position of women in science.

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As any early career researcher will know, attending your first big scientific meeting is a memorable event in your academic life. Last week, I was lucky enough to attend the Gordon Research Conference in Developmental Biology, held in sleepy South Hadley, two hours outside Boston, Massachusetts. For anyone who wasn’t local, the two hour drive from the airport to the conference site was an ordeal, but the welcome was worth it. The GRC ran an intensive scientific programme of seminars, discussion and poster sessions, held over five days. A Gordon Research Seminar (GRS) also ran over the weekend preceding the conference, exclusively for graduate students and postdocs to interact and present their research in a non-intimidating environment. Sessions spanned kingdoms, with researchers studying both animal and plant models. The themes were varied, and included evo-devo, organoids, and stem cells, as well as the usual suspects such as signalling and gene regulation.

In my opinion, running a conference with such a broad title was inspired. For a conference series where meetings often have very specific themes (browse through the list of past events on the GRC website and you will understand what I mean), running an event simply called ‘Developmental Biology’ drew people from all corners of the field. By keeping the title broad, no single mechanism or way of thinking dominated, and in fact several commonalities emerging in the talks were identified in the discussion. For example, the role of mechanical force in development was a recurring mechanism whether you worked on plants, Planarians or people! Perhaps the fact that this theme emerged despite no pre-meditated effort to select talks based around it, means it better reflects where the field is going and what questions are of interest to scientists.

Like at other GRCs, presentation of unpublished work was the star of the show. Speakers of all seniorities did a wonderful job of presenting new and exciting data and hypotheses, making a young researcher like me feel that I was learning things at the cutting edge.

The meeting was also useful to get feedback on published work too.

Publishing a paper can be a lonely experience. You spend years of your life perfecting and revising, then as soon as a manuscript is accepted and released you are left with an eerie silence, a vacuum, while the field digests the data. Apart from a smattering of mentions on social media, post-publication feedback from peers is virtually non-existent for biologists. Yet, when I arrived at the conference it was clear that people had read my paper. Some had even studied for their lab’s journal club! It meant something. Meetings such as the GRC give the community somewhere to exchange ideas. Not only are you there to present your research and absorb the work of others, but also to receive general and specific feedback from scientists across the community- who after all, are your target audience. Many of my most fruitful discussions and interactions happened over breakfast rather than during the seminar sessions themselves.

Several unsurprising topics kept cropping up in talk after talk. Developmental biologists have always been obsessed with pattern formation, and this is certainly not about to change. The field is moving towards computation, and molecular studies are becoming more and more sensitive as everyone who’s anyone seems to be doing single-cell RNA-seq!

Overall, the atmosphere at the meeting was friendly, fostering open discussion rather than feeling cliquey or competitive. Senior Professors and PhD students were free to interact, and did so. Talking about science, whether it was answering specific questions about my project, or talking about big challenges and how to approach them freed from the shackles of using a particular model organism, technique, or experimental design was fun!

By the end of the week, it is fair to say that the intense schedule began to take its toll, but everyone I spoke to was leaving having learned something, and having been surprised by something. To choose a single stand-out speaker would be impossible, but the quality of the talks were excellent. Even though the meeting was small, with perhaps fewer than one hundred attendees, the GRC did a great job at making researchers across disciplines feel part of the same community. The spirit of the conference was to share ideas, and I came away feeling inspired by people working in areas far removed from my own. After all, as developmental biologists, we are interested in the same fundamental questions, we just use different systems to answer them.

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