The construction of complex three-dimensional tissue structures during embryogenesis requires precise control of cell and tissue mechanics. The Xenopus embryo provides a powerful tool for interrogating this relationship, as demonstrated by a recent Development paper reporting the use of tissue explants to test predictions of mechanical models. We caught up with first author and recent graduate Joseph Shawky and his supervisor Lance Davidson, Professor in the Department of Bioengineering in the University of Pittsburgh, to hear more about the work.

Lance, can you give us your scientific biography and the questions your lab is trying to answer?

LD I arrived as a stranger in a strange land. My interests as a kid were a mix of collecting (perfect for biology) and astronomy (perfect for making). As many of my generation I wanted to be an astronaut and focused on physics and math through a BS in Physics at the University of Illinois and an MS in Space Science from York University in Toronto. I exited the academic stream for several years working as a scientific analyst in the nascent field of data science, but returned to earn a PhD in Biophysics from UC Berkeley. While at Berkeley I encountered radicals looking at the many roles of mechanics in biology, from the physics of virus capsid formation to the impact of waves on coastal kelp forests to the mechanics of sea urchin gastrulation. I had arrived in Berkeley as a theorist and left as an experimentalist. In my postdoc I cross-trained in amphibian embryology and cell biology. My mentors, Ray Keller and Doug DeSimone, were incredibly generous with training and tolerant of my digressions. They let me roam the embryo working on various processes ranging from neurulation to wound healing. In 2006 after an extended 8 year trip through the embryo, I took a faculty position in Bioengineering at the University of Pittsburgh. My group sits squarely between several cell and developmental biology labs and have we have terrific colleagues both at the University and at our neighbour institutions, Carnegie Mellon University.

We have two main questions in the lab and one area for technology development. The first question is “how do embryos work?” and by that I really mean the physical principle of work (force times distance), how forces are generated and how they shape tissues. My early experience as a theorist left me unsatisfied with the state of experimental embryology and we have consistently worked to develop tools and conceptual working models of morphogenesis. The second question is “why is development so robust?” This is a newer question to our group where we seek to understand how regulative programs of development integrate mechanical cues with conventional signalling and gene expression networks. This is an exciting new area for us and is leading in some surprising directions. The last topic, is much more focused on turning principles of development into tangible tissue engineering tools. The remarkable events of morphogenesis continually put tissue engineers to shame and we are trying to bridge that gap, both by training tissue engineers in concepts from morphogenesis, and in developing microfabrication tools to mimic embryonic tissue self-assembly.

And Joe, how did you come to join the Davidson lab, and what drives your research?

JS I joined the Davidson lab as an eager graduate student fascinated by the world of cell and tissue mechanics. It was through the research opportunities I had during my undergraduate and master’s studies that I became interested in pursuing my PhD in the field of developmental biomechanics. I was first introduced to cell culture during my undergraduate studies at Rensselaer Polytechnic Institute (RPI) where I investigated potential therapies for breast cancer. From there, I continued to study breast cancer at Cornell University but in a different context. I studied how cancer cells reorganize their extracellular matrix during cell migration. Here, I was introduced to techniques to measure forces and stresses on the nanometer scale. I became very interested in the various approaches to study cell mechanics and the ability to link mechanical properties with biological phenomena. When I was deciding where to complete my graduate work, I was impressed by the various devices and techniques developed in house at the Davidson Lab to probe cell and tissue mechanics and was also excited to study tissue mechanics within developing embryonic tissues.

Can you introduce the basics of the cellular solids model? Why are such material models useful for studying embryos?

JS&LD The cellular solids model (CSM) is a theoretical framework that relates the stiffness of cellular materials to the microstructure of component cells. CSM was developed to characterize the mechanical properties of open- and closed-cell materials, both synthetic and biological in origin. CSM describes how factors such as cellular density, cell wall thickness and mechanical material properties affect the bulk stiffness of cellular materials. In our study, we tested the basic premise of the CSM to investigate how different features including cell size and cortex properties might affect the bulk mechanical properties of embryonic tissues. This model was useful because it makes predictions and allowed us to test the contribution of features at different size scales to critical bulk properties. However, at its finest scale the basic equations of the CSM do tell us how F-actin microstructure, including organization and degree of cross-linking, may be influencing mechanical material properties. Such mechanical models are key to understanding the direct role of mechanics in shaping tissues as well as the indirect role of mechanical cues in providing positional information for development.

Can you give us the key results of the paper in a paragraph?

JS&LD In this study, our goal was to better understand the factors that contribute to bulk mechanics in Xenopus dorsal isolates and to shed light on possible mechanisms of stiffening during development. To formally make predications, we adapted the cellular solids model to embryonic tissues to predict how factors at different size scales may influence mechanics. We first confirmed the central assumption of the CSM, that tissue modulus does not depend on embedded structural elements, by engineering and mechanically testing a tissue devoid of large coherent 3D structures. We found that large-scale tissue architecture and cell size are not likely to influence bulk mechanical properties of early embryonic tissues. Our findings suggest that regulation of F-actin cortical thickness, density, and integrity plays a central role in regulating the physical mechanics of embryonic multicellular tissues.

What do you think explains the failure of ‘scrambled’ tissue explants to stiffen with age when cultured?

JS&LD Scrambled tissues were not able to reorganize or stiffen to the full extent of native tissues over time, suggesting that the organization of germ layers or germ layer tissue shape might be important for mechanical maturation. It remains unclear what aspects of architecture facilitate stiffening however could be organization of the ECM or in response to bulk morphogenesis movements. Fibronectin, the most abundant ECM protein during gastrulation and neurulation, does not directly contribute to mechanical properties as shown in a previous study from our lab however ECM may serve to align cells within the native stress field and lead to mechanical maturation.

Your paper seems exemplary of a very exciting time for mechanics in developmental biology. What are the main unanswered questions we should be tackling in the next decade?

(1) We have sparse experimental understanding of the mechanics of morphogenesis, gleaned from only a few model systems (fly, worm, frog, chick) with mechanically-accessible tissues (e.g. Drosophila epithelium, Xenopus explants), but know little about the lesions in human development that drive structural birth defects (e.g. spina bifida, congenital heart defects, cleft palate). How do these defects arise and are their ways they can be predicted and prevented?

(2) The mechanical microenvironment within embryos is largely hidden and has been the subject of long speculation but seldom the subject of rigorous experimental approaches. New technologies are removing the veil from these properties and allow us to start describing mechanical cues in embryos and testing how they may be involved in patterning.

(3) The field of tissue engineering arose from the needs of surgeons to reconstruct organs and tissues when regeneration and endogenous programs of healing fall short. More recently tissue engineers have begun to realize the remarkable robustness of developing tissues and organs. Harnessing evolved programs of self-assembly would open up an entirely new field where tissues and biological structures could be designed from the ground up in the same manner that electrical engineers design new circuits and civil engineers design new bridges. Co-opting the ‘technology’ of development would transform basic research, human health, and establish whole new industries.

When doing the research, did you have any particular result or eureka moment that has stuck with you?

JS One of the exciting moments in the lab was when we developed a process to generate viable and reproducible scrambled tissues. It took several design iterations and hours in the lab’s machine shop to develop a chamber and protocol that worked. These experiments were particularly exciting because it was an out of the box approach that allowed us to flip our research question on its head and tackle the question using a novel technique.

And what about the flipside: any moments of frustration or despair?

JS Early on it was challenging to identify techniques to alter cell size, particularly decreasing cell size, without disrupting development. We tried several approaches including removing cytoplasm from the single cell embryo. Once we got focused on manipulating cell cycle we were able to find reliable ways to inhibit and accelerate the cell cycle and generate tissues with increased and decreased cell density.

So what next for you Joseph after this paper?

JS I’ve since graduated from the Davidson lab and completed a medical device policy fellowship at the U.S. Food and Drug Administration. Now, I am currently working as a Strategy and Analytics Consultant supporting clients within government health agencies.

Where will this work take the Davidson lab?

LD The Xenopus embryo provides unparalleled access to the mechanics of morphogenesis and allows us to test ideas that folks working with other models would think preposterous. By focusing on the most elementary of tissue movements, convergent extension of the dorsal axis, we have been free from confounding changes in cell identity and 3D reorganizations that drive more complex morphogenesis movements. We are now applying tools and theoretical frameworks developed from this work to expose cryptic mechanical cues and their roles in shaping organs such as the heart, skin, and cardiovascular network.

Finally, let’s move outside the lab – what do you like to do in your spare time in Pittsburgh?

LD I enjoy early morning dog walks through the forested city parks of Pittsburgh and lead a domestic life of cooking and gardening, but really I love spending free time in the lab since it is full of microscopes, mechanical gadgets, and frogs and there are so many open questions about embryonic development.

JS My favorite things to do in Pittsburgh are long bike rides on the beautiful riverside trails and enjoying the vibrant restaurant scene. Aside from biking and eating, I also enjoy grilling, hanging out with friends and a good podcast.

Multiscale analysis of architecture, cell size and the cell cortex reveals cortical F-actin density and composition are major contributors to mechanical properties during convergent extension. Joseph H. Shawky, Uma L. Balakrishnan, Carsten Stuckenholz, Lance A. Davidson
Development 2018 145: dev161281 doi: 10.1242/dev.161281

This is #51 in our interview series. Browse the archive here.

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The Department of Biology within the College of Natural and Health Sciences at The University of Tampa invites applications for a full-time tenure-track position in developmental biology beginning in August 2019.

The University of Tampa is a medium-sized, comprehensive, residentially based private institution of 9,200 undergraduate and graduate students. The University is ideally situated on a beautiful 110-acre campus next to the Hillsborough River, adjacent to Tampa’s dynamic central business district, which is a growing, vibrant, diverse metropolitan area. UT reflects this vibrancy; with 22 consecutive years of enrollment growth UT boasts 260 student organizations, a multicultural student body from 50 states and 140 countries and “Top Tier” ranking in U.S. News & World Report.

Teaching responsibilities will include introductory biology for majors, an upper division course in developmental biology, and other courses as needed. The department is interested in attracting a broadly trained biologist with expertise in developmental biology. The candidate is expected to engage in research activities that involve undergraduates and yield peer-reviewed publications. Limited start-up packages and modest research space are available for tenure-track positions.

PhD required, ABD candidates considered, with prior teaching and research experience with undergraduates desirable.

Review of applications will begin October 10, 2018, and continue until the position is filled.

For further details and to apply, please visit our website at www.ut.edu/jobs                                                                              

The University of Tampa is an equal opportunity/affirmative action employer dedicated to excellence through diversity and does not discriminate on the basis of age, race, sex, disability, sexual orientation, national origin, religion, marital status, gender identity, veteran status or any other non-job related criteria. The University of Tampa recognizes the importance of a multicultural community of students, faculty, and staff who seek to advance our commitment to diversity. The University invites applications from underrepresented groups and those who have academic experiences with diverse populations.

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We are looking for ambitious and motivated postgraduate candidates to join the new computational biology group, led by Dr. Linus Schumacher, at the MRC Centre for Regenerative Medicine in Edinburgh. The group is using expertise in mathematical modelling of cellular processes in development and collective behaviour in biological systems, with a recent focus on stem cells and regeneration.

There is one fully-funded position (UK/EU/overseas) focussing on mathematical & computational modelling of stem cell populations in regeneration and experimentally relevant predictions. Find out more here: https://www.findaphd.com/search/ProjectDetails.aspx?PJID=101556

A second position is jointly experimental and computational, in collaboration with Val Wilson’s lab, on cell state transitions in differentiating embryonic stem cells. This position is competitively funded and available through the EastBio doctoral training programme. Find out more here: http://www.eastscotbiodtp.ac.uk/modelling-cell-state-transitions-differentiating-embryonic-stem-cells

Further opportunities are available through the University of Edinburgh’s Wellcome Trust funded Tissue Repair postgraduate training programme. Students in this programme will have the opportunity to do research rotations and PhDs with our group (in joint supervision with experimental labs).

This is an opportunity to conduct your PhD research on mathematical and computational biology, embedded in a world-leading centre for multidisciplinary research in mammalian stem cell biology and regenerative medicine. Find a list of all PhD opportunities here: http://crm.ed.ac.uk/join-us/phd-training/phd-opportunities

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The MRC Weatherall Institute of Molecular Medicine (WIMM) has fully funded 4-year Prize PhD (DPhil) Studentships available to start in October 2019. These Studentships are open to outstanding students of any nationality who wish to train in experimental and/or computational biology.

The Institute is a world leading molecular and cell biology centre that focuses on research with application to human disease. It includes the recently opened MRC WIMM Centre for Computational Biology and houses over 500 research and support staff in 50 research groups working on a range of fields in Haematology, Gene Regulation & Epigenetics, Stem Cell Biology, Computational Biology, Cancer Biology, Human Genetics, Infection & Immunity. The Institute is committed to training the next generation of scientists in these fields through its Prize PhD Studentship Programme.

The fully funded studentships include a stipend of £18,000 per annum and cover University and College fees.

Further information on the studentships, how to apply, and the projects available can be found at:

http://www.imm.ox.ac.uk/studentships19

Closing date for submission of applications:  Friday, 11 January 2019, 12 noon (UK time).

Interviews will take place the week commencing 28 January 2019.

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By Sera Moon Busse

Studying limb regeneration in model organisms is important for the advancement of regenerative medicine in humans. We set out to study regeneration in the hind limbs of the African Clawed Frog Xenopus laevis – this animal is able to regenerate its hind limbs very early in development, but it loses this ability during metamorphosis. Additionally, there is a large and still growing body of evidence suggesting that charged particles called ions (for example, sodium, potassium, and chloride) are important for regulating pathways that control growth and regeneration. Though a relatively small number of biologists’ work is centered around this field, called bioelectricity, its implications thus far in the fields of developmental biology and regenerative medicine have been compelling. As an undergraduate, I had the privilege to be trained and to perform research in a lab that is at the forefront of this field, which had many unanswered and yet unresearched questions.

We – being myself and my team of mentors, Dr. Patrick McMillen and Professor Michael Levin, who were both Tufts undergraduates ten and twenty years before me, respectively – married the concept of bioelectrics and Xenopus hind limb regeneration to ask the question: what bioelectric changes do younger, regenerating froglets exhibit in response to amputation that older, non-regenerative tadpoles do not? This is part of the lab’s mission to discover regenerative therapies, based on manipulating bioelectric signaling, for various biomedical applications. We amputated the limbs of both regenerating tadpoles and non-regenerating tadpoles, and soaked them in a solution containing a molecule that glows in response to changing ion concentrations across cell membranes, also called membrane potential. By the time we were ready to analyze the results of this work, the product of observation and the scientific method led us to a bigger, more perplexing question to answer.

In performing these initial experiments, I did what I believed was my due diligence as a researcher: I needed controls! So I used the contralateral, uncut limbs of the froglets as controls, a common method used across many fields, to make sure the dye wasn’t being randomly soaked up by cells and to establish a baseline background for what the fluorescence would look like in un-injured, intact tissues. In fact, I quickly found that the dye was being taken up by cells in the contralateral limb, but only in the intact limbs of frogs that had the other limb amputated. Un-amputated froglets did not exhibit staining from the dye in either limb. I took this information to my mentors, sure that they would already have an explanation prepared, as professors and teachers before them always had when a question arose in lecture. For the first time in my academic career, nobody had an answer for me. This phenomenon had never been observed before, therefore nobody had asked the question; there was truly no one with an answer.

It is at this point in many young scientists’ careers that the potentially interesting project is swooped out from under them, their mentors realizing the value of the new findings, hungry for the credit. For others, their mentors do support intellectual curiosity and give them the freedom to pursue their own projects, but their projects do not see the light of day because there simply are not enough resources. For these reasons, the Tufts biology department, and more specifically, the Levin lab, are extremely unique. I could not have been more fortunate, because I was given both the freedom to head my own project and the resources to do so.

Ultimately, we found that the contralateral limbs of regenerating tadpoles glowed (in the presence of that molecule I mentioned earlier) in a region on the contralateral limb that very closely mirrors the plane of amputation. Our data revealed that the un-injured limb somehow knows the relative location (and even type) of injury, within about 30 seconds (Busse et al. Development 2018; doi:10.1242/dev.164210). This phenomenon has interesting implications for regenerative medicine. What we found is a distal region that not only recognizes, but also encodes information about an injury incurred by the body. If similar signaling phenomena can be found in mammalian systems, there is potential for the development of surrogate site diagnostics – looking at one site to decipher information about the health of another. This information is also evidence that contralateral limbs are not an appropriate control for experiments, and hopefully encourages everyone to think twice before using them as controls!

There are many more questions that we intend to answer in the future; for example, how does one part of the body sense that another part of the body has been injured? In the meantime, the context of this research is extremely important for anyone in any field of research to understand. I asked a question that nobody at the time could answer, and was given the opportunity to find an answer. The result was that I learned more collaborating with Dr. Patrick McMillen, Professor Michael Levin, and many others in the Levin lab than any biology course could have taught me. Many students are prompted to spend time answering questions throughout the duration of their degree, but I was encouraged to ask them, and it has fundamentally changed the way I think about learning. I had teachers who were not eager to prove what they knew, but rather who were eager to teach how they knew it.

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The Turing Centre for Living Systems is seeking a highly motivated research engineer to fill the post of ‘leading data scientist/data analyst’, within CENTURI’s technology transfer platform. This position will be a central point of data analysis, data sharing and code sharing of our research community.

Three-year contract from the Aix-Marseille Université.

Deadline for Application: November 23

Applications should include:

• a CV (including a list of publications)
• a cover letter (describing past experience with data analysis)
• two recommendation letters

More info and to apply: http://centuri-livingsystems.org/job-offer-data-analyst/

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Applications are open for the Wellcome Trust funded four year PhD programme in Developmental Mechanisms at the University of Cambridge.  We are looking for talented, motivated graduates or final year undergraduates, and are keen to attract outstanding applicants in the biological sciences, who are committed to doing a PhD.  We are able to fund both EU and *non-EU students.

Closing date:  Thursday 3 January 2019 (by 12:00pm midday UK time)

For more details about the application process and the programme please see the website:

http://devmech.pdn.cam.ac.uk/phd/index.html

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A postdoctoral position is available in the laboratory of Dr. Sophie Astrof at Rutgers University to study roles of cell-extracellular matrix (ECM) interactions in cardiovascular development and congenital heart disease. We have recently discovered that progenitors within the second heart field (SHF) give rise to endothelial cells composing pharyngeal arch arteries (Dev Biol 421:102–111, 2017). Projects in the lab focus on the role of ECM in regulating the development of SHF-derived progenitors into endothelial cells and their morphogenesis into blood vessels. The successful candidate will combine genetic manipulation, embryology, cell biology, and confocal imaging to study molecular mechanisms by which cell-ECM interactions and tissue microenvironment regulate cardiovascular development. Additional projects focus on the investigation of cell type-specific and cell-autonomous functions of fibronectin in development and signaling (Development 143:88-100, 2016). Interested candidates should send their CV and the names of three references to Sophie.astrof@rutgers.edu

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Jeff Rasmussen tells the story behind his recent paper from the Sagasti Lab in Dev Cell.

This project began as an extension of my earlier postdoc work in Alvaro Sagasti’s lab investigating removal of axon debris following skin injuries in the larval zebrafish [1] and led me into scientific territory that I never anticipated. It is a story that would not have happened without open-mindedness, encouragement and—most importantly—help from colleagues in the fish community.

Sensory axon endings profusely innervate the skin, and skin injuries trigger axon degeneration. We previously discovered that keratinocytes are the primary phagocyte for degenerating axons in larval skin. But what cells eat axons that degenerate in the more complex adult skin?

In order to answer this question, I first needed a way to visualize sensory axons in adults. Most work in zebrafish has focused on the larval system, so markers for adults have lagged behind. Luckily, I came across a transgenic line made by a previous graduate student in Alvaro’s lab [2] that showed bright and specific expression of sensory axons in adults. The pattern of adult skin innervation revealed by this line caused this project (and my career) to take a twist.

A Striking Axon Pattern

Axons of Rohon-Beard neurons innervate most of the larval fish skin. Rohon-Beard axons in the skin rarely bundle (fasciculate). By contrast, this transgenic line revealed that axons of dorsal root ganglion (DRG) neurons, which innervate adult skin, were frequently bundled. More surprisingly, these bundles were evenly spaced across the surface of scales, which underlie the adult epidermis (Figure 1). Alvaro whole-heartedly encouraged me to dig deeper into what created these evenly spaced bundles, despite his lab having no experience working with post-embryonic stages.

Thi’s Developmental Studies

Thi Vo, an undergraduate researcher in Alvaro’s lab, took on the challenge of analyzing post-embryonic development. Because many Rohon-Beard neurons die after only a few days of development, we expected that DRG axons would innervate the epidermis shortly thereafter. However, by staining isolated scales to visualize axons, Thi found that the axon bundles only appeared during late juvenile stages. So Thi next analyzed mutants lacking DRG neurons and found that the bundles never formed, proving that they were indeed DRG axons.

Thi also stained scales with phalloidin to visualize cell morphology and found that a set of elongated cells apparently presaged the path of the axon bundles. What could these cells be?

Lindsey’s Schwann cells

We initially hypothesized that the elongated cells were Schwann cells, the glia of the peripheral nervous system. Schwann cells are neural-crest derived, and Shannon Fisher’s group recently made a neural crest lineage reporter [3], which we learned was growing in Gage Crump’s lab at USC. To determine if the line labeled Schwann cells in adults, I made a trip across town to visit Lindsey Barske, a postdoc in the Crump lab, who was working with the neural crest reporters. One of Lindsey’s lines labeled Schwann cells coating the axon bundles, showing that they are nerves and giving us a key reagent to visualize their development. But when Thi and I analyzed the timing of Schwann cell migration, they appeared too late to pioneer the path of the DRG bundles, ruling out this hypothesis.

Michael’s Vessels

After hearing about our work at a Southern California Zebrafish Meeting, Michael Harrison, a postdoc in Ellen Lien’s lab working on heart and vascular development, suggested we analyze several of his chemokine mutants. Thi and I took a bus trip down Sunset Blvd to CHLA to collect scales from these mutants. Although this effort was ultimately fruitless, as luck would have it, Michael’s mutants expressed multiple transgenic reporters. One of these transgenes was fli1a:EGFP (a vascular reporter made by Brant Weinstein’s group) [4], which revealed that the axon bundles tightly associated with blood vessels (Figure 1). This was unexpected because we had initially ruled out a vascular contribution based on analysis of a vessel reporter not as broadly expressed as fli1a.

Intriguingly, axons and vessels also tightly associate in mammalian skin and axons promote vascular remodeling and arterial differentiation in mouse [5]. Were blood vessels the elongated cells that arose early in scale development? No, since we found that blood vessels only appeared along mature scales, once animals reached adulthood. What about the converse: did axons pattern the vessels? By again analyzing mutants lacking sensory neurons, we found that blood vessels appeared normal. Thus, in contrast to mammals, skin nerves and vasculature are independently patterned in fish. This was an important finding but, once again, the identity of the pioneering cells remained elusive.

Sandeep’s Osteoblasts

The scale surface is made from bone and contains a number of striking patterns. Remarkably, we noticed that the axon bundles and vessels aligned with scale radii, grooves in the bone that radiate from the scale center (Figure 1). Could osteoblasts, bone-forming cells, or osteoclasts, bone-degrading cells, guide axons and vessels? We first examined osteoclasts but found no evidence that they form the radii. Next, I made another crosstown trip to the Crump lab—this time with the help of Sandeep Paul—to look at osteoblast reporters. Sandeep’s lines showed that osteoblasts line mature radii, as suggested by pioneering ultrastructural studies [6, 7]. Imaging osteoblasts early in scale development revealed that they create the radial paths by polarized migration.

To test if osteoblasts promote skin innervation during regeneration, we used an inducible osteoblast ablation line made by Ken Poss’ group [8] and found that blocking scale regeneration by osteoblast ablation resulted in a reduction of axon density. To test if scale development similarly promoted innervation, we analyzed mutants that prevent scale development [9, 10]—provided as part of a “scale care package” by Matt Harris’ lab. These mutants had reduced skin innervation and vascularization, showing that scales are also required during ontogeny.

Full Scale Ahead

Although I never planned to work on scales as a model system, I am really excited about the potential for these mini-organs to reveal the cellular and molecular basis for cell type patterning during skin development and repair—questions that I will be pursuing in my newly formed research group at the University of Washington. Scales are evolutionarily related to other types of specialized skin appendages like feathers and hair. Thus, studies of fish scales may reveal general mechanisms for coupling organ maturation and growth to skin patterning. Scales may also yield insights into bone-nerve interactions that occur in diverse tissues, like antlers, teeth and long bones. An increasing number of genetic tools, together with advances in live-cell imaging of post-embryonic stages (Figure 2), suggest the future is bright for a resurgence of scales as a model system.

References

[1] Rasmussen JP, Sack GS, Martin SM, Sagasti A. Vertebrate epidermal cells are broad-specificity phagocytes that clear sensory axon debris. J Neurosci. 2015;35(2):559–70.

[2] Palanca AMS, Lee SL, Yee LE, Joe-Wong C, Trinh LA, Hiroyasu E, et al. New transgenic reporters identify somatosensory neuron subtypes in larval zebrafish. Dev Neurobiol. 2013;73(2):152–167.

[3] Kague E, Gallagher M, Burke S, Parsons M, Franz-Odendaal T, Fisher S. Skeletogenic fate of zebrafish cranial and trunk neural crest. PLoS One. 2012;7(11):e47394.

[4] Lawson ND, Weinstein BM. In vivo imaging of embryonic vascular development using transgenic zebrafish. Dev Biol. 2002;248(2):307–18.

[5] Mukouyama Ys, Shin D, Britsch S, Taniguchi M, Anderson DJ. Sensory nerves determine the pattern of arterial differentiation and blood vessel branching in the skin. Cell. 2002;109(6):693–705.

[6] Waterman RE. Fine structure of scale development in the teleost, Brachydanio rerio. Anat Rec. 1970;168(3):361–379.

[7] Sire JY, Allizard F, Babiar O, Bourguignon J, Quilhac A. Scale development in zebrafish (Danio rerio). J Anat. 1997;190 ( Pt 4):545–561.

[8] Singh SP, Holdway JE, Poss KD. Regeneration of amputated zebrafish fin rays from de novo osteoblasts. Dev Cell. 2012;22(4):879–886.

[9] Harris MP, Rohner N, Schwarz H, Perathoner S, Konstantinidis P, Nusslein-Volhard C. Zebrafish eda and edar mutants reveal conserved and ancestral roles of ectodysplasin signaling in vertebrates. PLoS Genet. 2008;4(10):e1000206.

[10] Rohner N, Bercsenyi M, Orban L, Kolanczyk ME, Linke D, Brand M, et al. Duplication of fgfr1 permits Fgf signaling to serve as a target for selection during domestication. Curr Biol. 2009;19(19):1642–1647.

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1 PhD Position : Characterization of Hedgehog morphogens in vitro and in vivo

Hedgehog (Hh) morphogens play important roles in development and cancer, but their mode of extracellular transport to target cells is only poorly understood. Thus, we aim at the characterization of various unusual posttranslational regulatory mechanisms in Hh biology, such as Hh multimerization on the surface of secreting cells via structural and biochemical analysis of Hh clusters, and the unusual mode of Hh transport and gradient formation.

We use a wide range of biochemical methods, such as recombinant protein production and chromatographic/functional characterization of proteins and Heparan sulfate-proteoglycans (HSPGs), determination of Shh/HSPG binding and in vivo testing of any obtained models of protein association and transport (In Drosophila melanogaster).

We invite applications from highly qualified and motivated students of any nationality. The applicant will hold a Masters degree (Biology, Chemistry, Biotechnology, Pharmacy or Biochemistry) and has gained first biochemical research experience. Experience in Drosophila experimentation is highly welcome, but not required. The successful applicant will find strong support within the excellent interdisciplinary environment of the SFB1348 of the University of Muenster.

Additional information can be found here:

https://www.medizin.uni-muenster.de/physiolchem.html

and here:

http://sfb1348.uni-muenster.de/

Starting date: at or around 1.1.2019 at the applicants convenience.

Timeframe: 3 years

Payment: 1 PhD contract (TV-L E13 65%, approximately 2300€ before taxes)

Interested? Please apply electronically to Prof. Dr. Kay Grobe, kgrobe@uni-muenster.de

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