The origin of paired fins is a major unresolved issue in vertebrate evolutionary biology, and has been a topic of debate among palaeontologists, comparative anatomists and developmental biologists for over a century. Central to any question of “evolutionary origins” is the concept of homology: the sharing of features due to common ancestry. Homology may explain the existence of shared features between organisms (historical homology – e.g. the arms of a chimpanzee and the arms of a human are homologous because these structures have been retained from a common ancestor that possessed arms), or the existence of shared features within an organism (serial homology – e.g. the vertebral elements within a human, which exhibit a range of morphologies, but which nevertheless share a common underlying ground plan) (Roth, 1984; Wagner, 1989). In either case, homology reflects a continuity of anatomical, cellular, or genetic information, and provides a useful conceptual framework for investigating the evolutionary relationship among body plan features in distantly related taxa (Van Valen, 1982).

Cartilaginous fishes (sharks, skates, rays and holocephalans) are unique among living jawed vertebrates, in that they possess a series of skeletal appendages called branchial rays that project laterally from their gill arches (Fig. 1a). These branchial rays articulate with the gill arch cartilages in a way that is broadly reminiscent of the articulation between pectoral fins or limbs and the shoulder girdle, and this similarity led the comparative anatomist Carl Gegenbaur to propose that paired fins and limbs evolved by transformation of a gill arch (Gegenbaur, 1878) (Fig. 1b, c) – a hypothesis of serial homology that remains controversial to this day. Unfortunately, the fossil record currently tells us relatively little about the stepwise acquisition of paired fins during vertebrate evolution, so we decided to address this question from a developmental perspective. We were interested in determining whether the anatomical parallels that Gegenbaur noted between the gill arches of cartilaginous fishes and fins/limbs may reflect common underlying molecular patterning mechanisms in these organ systems. To this end, we conducted a series of experiments to investigate branchial ray patterning in embryos of an oviparous (egg-laying) cartilaginous fish, the little skate, Leucoraja erinacea (see video below for an overview of skate embryonic development).

It might be helpful to first briefly introduce the gill arch, and how the gill arches of cartilaginous fishes are unique relative to those of other jawed vertebrates. All vertebrate embryos possess a bilateral series of pharyngeal arches on the sides of their developing head (Fig. 2a), and the mesenchyme within these arches gives rise to much of the craniofacial skeleton. The first pharyngeal arch is called the mandibular arch, the second is called the hyoid arch, and this is followed by a variable number of gill arches (most cartilaginous fishes have five gill arches). Primitively, the mandibular arch gave rise to the jaw skeleton, the hyoid arch gave rise to the skeletal apparatus that suspends the jaw from the braincase, and the gill arches give rise to the skeletal supports of the respiratory apparatus of the gills. These skeletal derivatives are conserved in a relatively primitive organisation in cartilaginous fishes, but are also present in other vertebrates (though often in a derived state – for example, the skeletal derivatives of the “gill arches” of mammals give rise to the laryngeal skeleton). Uniquely, though, in cartilaginous fishes, once the hyoid and gill arches have formed, they undergo a lateral expansion (Fig. 2b), and give rise to an additional set of skeletal elements – the branchial rays – that project laterally from the arches (Gillis et al., 2009). These branchial rays ultimately provide skeletal support to the fleshy flaps that protect the gills of cartilaginous fishes. As appendages, branchial rays must be patterned along the proximodistal axis (as they expand laterally) and also along the anterior-posterior axis (branchial rays exhibit a pronounced anterior-posterior polarity, and articulate proximally along the posterior margin of the hyoid and gill arch cartilages). In our paper (Gillis and Hall, 2016), we were interested in testing whether skate gill arches deploy similar axial patterning mechanisms as do fins and limbs (as would be predicted by an hypothesis of gill arch-fin/limb serial homology).

In this study, we focused our attention on the sonic hedgehog (Shh) signaling pathway, as the axial patterning function of this pathway during limb development is very well understood. Decades of experimental embryological and molecular investigation have revealed that Shh signaling is important in both anterior-posterior patterning of the limb, and in the proliferative expansion of limb skeletal progenitors. Classical chick embryo experiments by Saunders and Gasseling (1968) demonstrated that upon transplantation of donor posterior limb bud mesenchyme to the anterior region of a host limb bud, the resulting limb will form an additional set of digits that are oriented mirror-image to the normal digits (Fig. 3a). This posterior limb bud signaling centre is known as the zone of polarizing activity (ZPA). Twenty five years later, the Tabin lab demonstrated that Shh was the polarizing signal that was being secreted by the ZPA (Fig. 3b,c), and that misexpression of Shh in the anterior limb bud was sufficient to induce the ectopic, mirror-image digits noted by Saunders and Gasseling (Fib. 3d,e) (Riddle et al., 1993). In addition to this anterior-posterior patterning role, Shh signaling is also required for the expansion of limb endoskeletal progenitors, and progressively earlier loss of Shh signaling during limb development results in a progressively more profound deletions of distal limb skeletal elements (as shown, for example, by the genetic deletion of Shh from mouse limb buds, or by pharmacological manipulation of hedgehog signaling in chick and salamander) (Fig. 3f) (Towers et al., 2008; Zhu et al., 2008; Stopper and Wagner, 2007). Does Shh signaling function in a similar manner during the development of skate branchial rays?

We first sought to determine whether Shh signaling components were expressed during skate gill arch development. mRNA in situ hybridization experiments revealed that, indeed, Shh is expressed in a polarized pattern during the development of the skate hyoid and gill arches – initially in the posterior epithelium of each arch, and eventually in an epithelial stripe along the leading edge of the hyoid and gill arches as they undergo lateral expansion (Fig. 4). When we looked at the expression of Ptc2 (a transcriptional readout of Shh signaling), to determine which tissues are responding to this Shh signal, we observed expression in both the distal gill arch epithelium, and in the mesenchyme beneath the Shh expression domain (Fig. 4). One key difference, of course, is that in skate gill arches, Shh is expressed in posterior-distal epithelium, while in the limb bud, Shh is expressed in posterior mesenchyme. However, in both cases, Shh signal is transduced in overlying epithelium and distal mesenchyme (so although the source of the signal is different between these appendages, the responding tissues are similar).

In order to determine whether Ptc2+ mesenchymal cells (i.e. mesenchymal cells responding to Shh signal) ultimately contribute to the branchial ray skeleton, we conducted a fate mapping experiment. Over the past several years, I have developed protocols for the experimental manipulation and long term in/ex ovo culture of skate embryos, and this now allows us to conduct targeted embryonic manipulations (e.g. by microinjecting and surgically manipulating specific regions of the embryo) and to focally label populations of embryonic cells, in order to trace the long-term fates of their progeny (Fig. 5a,b). For this experiments, we microinjected the lipophilic dye CM-DiI immediately subjacent to the Shh-expressing epithelium of the gill arch, so that we could assess the contribution of these cells (and their progeny) to the gill arch skeleton. CM-DiI is readily incorporated into cell membranes, and is retained in daughter cells through mitosis (although diluted somewhat with each round of cell division). Importantly, though, CM-DiI will persist through fixation and paraffin sectioning, and so upon skeletal differentiation, we can use fluorescent microscopy on thin sections to recover even very small specks of membrane-localized CM-DiI (indicating decent from mesenchymal cells that were Shh-responsive earlier in development). These experiments demonstrated that Shh-responsive gill arch mesenchyme does contribute to branchial rays (Fig. 5c), and suggest that this signaling pathway may be directly influencing the behaviour and fate of branchial ray progenitors.

Finally, to test the function of Shh signaling during skate branchial ray development, we conducted a series of in ovo pharmacological treatments. Skate embryos develop in large, leathery egg shells, and are amenable to bath treatment by in ovo injection of small molecules. We used cyclopamine – a small molecular inhibitor of the hedgehog signaling pathway – to inhibit Shh signaling at different stages of gill arch development, and to test for stage-specific roles for Shh signaling in bronchial ray patterning. We chose three stages for treatment: stage 22 (gill arches have still formed, and Shh is expressed in posterior arch epithelium), stage 27 (gill arches are undergoing lateral expansion, with Shh signaling resolved to an epithelial stripe along the leading edge of the expanding arch) and stage 29 (just prior to the condensation of the gill arch endoskeleton). Interestingly, upon manipulation of Shh signaling at these different stages of gill arch development, we observed branchial ray defects that were broadly reminiscent of the skeletal defects observed upon manipulation of Shh signaling during limb development. For example, we observed that progressively earlier inhibition of Shh signaling resulted in a progressively greater deletion of branchial rays (i.e. cyclopamine treatments at stages 22 and 27 resulted in a significant reduction in the number of branchial rays on each arch, while treatment at stage 29 resulted in no significant difference in branchial ray number) (Fig. 6a). We also observed that cyclopamine treatment at stage 22 resulted in loss of anterior-posterior axis specification (i.e. the few branchial rays that did form articulate down the midline of the arch, rather than along the posterior margin of the arch) while cyclopamine treatment at stages 27 or 29 had no effect on the anterior-posterior axis (Fig. 6b). It therefore appears that, as in the limb bud, Shh signaling functions initially in skate gill arches to establish the anterior-posterior axis, and subsequently to maintain proliferative expansion of branchial ray endoskeletal progenitors.

So what does this shared role for Shh signaling in gill arch and limb bud patterning mean? It is possible that limbs share a patterning mechanism with gill arches because these structures are, indeed, transformational homologues (i.e. fins and limbs evolved by transformation of a gill arch in an ancestral vertebrate, as proposed by Gegenbaur). However, it may also be that gill arches and fins/limbs have independently recruited a deeply conserved “core” appendage patterning mechanism (i.e. parallel evolution, leading to serial homology), or that gill arches and fins/limbs are convergently using the Shh signaling pathway for similar purposes. Only palaeontological data can tell us about anatomical transitions, and such data are needed in order to formally test Geganbaur’s hypothesis of gill arch-paired fin transformational homology. However, it is now clear that some of the anatomical parallels that led Gegenabur to propose his gill arch hypothesis of fin origins reflect common underlying patterning mechanisms, and further investigation of the molecular basis of branchial ray patterning in cartilaginous fishes will allow us to determine whether these common mechanisms are the result of parallel evolution or convergence. I think that this study sets out an exciting path forward to address the origin and evolution of paired appendages in vertebrates, and highlights how complementary palaeontological and developmental approaches are needed in order to truly address the big, unanswered questions in vertebrate body plan evolution.

References

Gegenbaur, C (1878) Elements of Comparative Anatomy. London, UK: Macmillan.

Gillis, J.A., Dahn, R.D. and Shubin, N.H. (2009) Chondrogenesis and homology of the visceral skeleton in the little skate, Leucoraja erinacea (Chondrichthyes: Batoidea). J. Morphol. 270, 628-643.

Gillis, J.A. and Hall, B.K. (2016) A shared role for sonic hedgehog signalling in patterning chondrichthyan gill arch appendages and tetrapod limbs. Development 143, 1313-1317.

Owen, R. (1866) Anatomy of Vertebrates I. Fishes and Reptiles. London, U.K.: Longmans, Green, and Co.

Riddle, R.D., Johnson, R.L., Laufer, E. and Tabin, C.J. (1993) Sonic hedgehog mediates the polarizing activity of the ZPA. Cell 75, 1401-1416.

Roth, V.L. (1984) On homology. Biol. J. Linn. Soc. 22, 13-29.

Stopper, G.F. and Wagner, G.P. (2007) Inhibition of Sonic hedgehog signaling leads to posterior digit loss in Ambystoma mexicanum: parallels to natural digit reduction in urodeles. Dev. Dyn. 236, 321-331.

Towers, M., Mahood, R. Yin, Y. and Tickle, C. (2008) Integration of growth and specification in chick wing digit patterning. Nature 452, 882-886.

Van Valen, L.M. (1982) Homology and causes. J. Morphol. 173, 305-312.

Wagner, G.P. (1989) The biological homology concept. Annu. Rev. Ecol. Syst. 20, 51-69.

Zhu, J., Nakamura, E., Nguyen, M.T., Bao, X., Akiyama, H. and Mackem, S. (2008) Uncoupling sonic hedgehog control of pattern and expansion of the developing limb bud. Dev. Cell. 14, 624-632.

(6 votes)

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Here are the highlights from the current issue of Development:

The origins of lung macrophages revealed

Tissue-resident macrophages are phagocytic cells that are essential for the response to injury and infection. Both within and between tissues, macrophages can show distinct characteristics, but are these attributes developmentally defined or determined by the microenvironment? In the mouse lung, there are two distinct macrophage populations: alveolar macrophages that reside within the lumen of the alveoli and interstitial macrophages that occupy the interalveolar space and elsewhere in the lung parenchyma. Some studies have suggested that alveolar macrophages originate from and are repopulated by an interstitial macrophage precursor, while others indicated that they can maintain themselves independently. Serena Tan and Mark Krasnow (p. 1318) now show that there are in fact three developmentally distinct lineages that populate the lung in three waves, with minimal interconversion between them – at least under homeostatic conditions. The first population, derived from yolk sac haematopoietic cells, populate the interstitial space in embryogenesis, but become confined to peripheral and perivascular regions postnatally. The second, of as-yet-unknown origin, initially occupy the interstitium but then become alveolar macrophages. The third population enters the lung postnatally from circulating monocytes and constitute the majority of mature adult interstitial macrophages. In the lung at least, it appears that developmental origin, rather than environmental influence, is the primary determinant of macrophage identity and diversity.

Transcription without TBP

The canonical mechanism of transcription initiation in all metazoans involves recruitment of TATA-binding proteins (TBP, TLF or TBP2 in vertebrates) to the promoter, as a rate-limiting step before binding of RNA polymerase II. TBP, TLF and TBP2 have non-redundant functions, but the degree of redundancy between them is not clear; nor is it well understood whether there are TBP-independent mechanisms of transcription initiation in vivo. On p. 1340, Gert Veenstra and co-workers now show that, during early Xenopus development, there is a small group of genes whose transcription is independent of all TBP family members (denoted TBP family-insensitive or TFI genes). These genes are enriched for factors expressed in mesoderm and at Spemann’s organiser and include several key transcription factors involved in mesendoderm specification. Strikingly, most TFI genes are bound by these TFI transcription factors. Gcn5, a component of the SAGA complex thought be involved in non-canonical transcription initiation, is recruited to TFI promoters upon TBP family knockdown, is not required for their transcription in the presence of TBP-related factors, but seems to compensate in their absence. This work provides clear evidence that alternative mechanisms of transcription initiation exist in vivo, and that they may be preferentially used for a particular set of key developmental genes.

Completing the neuroblast map

In the developing Drosophila embryonic central nervous system (CNS), the pattern of neural stem cells – neuroblasts (NBs) – is highly stereotyped, both between individuals and, in the truncal ventral nerve cord, between segments. Over the past decades, multiple studies have mapped the spatio-temporal origin and gene expression signature of the embryonic NBs in the brain, thorax and abdomen. On p.1290, Rolf Urbach and colleagues provide the final piece to this puzzle by providing a comprehensive map of the NBs in the gnathal (labial, maxillary and mandibular) segments of the embryo. In doing so, they are able to compare the NBs complement of each segment to identify homologies between NBs in different embryonic origins. Their work demonstrates the progressive loss of NBs from trunk to progressively anterior gnathal segments and analyses its cause. Despite the reduced NB number, homologies in developmental origin and expression pattern are clearly recognisable, and can also be traced into posterior brain segments. The wealth of data in this and related papers provide an essential foundation to understand the molecular and evolutionary basis of segmental diversification of the CNS.

Vascular development in technicolour

During development, the vascular endothelium becomes covered by mural cells (MCs) – vascular smooth muscle cells or pericytes – that are essential for vascular stability and homeostasis. MCs are known to be of mesodermal or neural crest origin, but little is known about how they are recruited to and cover the vessels – primarily because live imaging of this process has been challenging. Now (p.1328), Shigetomo Fukuhara, Naoki Mochizuki and colleagues overcome this hurdle by developing transgenic zebrafish lines to mark MCs fluorescently. They then use these tools to follow the origin and subsequent behaviour of MCs in both cranial and trunk regions of the embryo. The authors find that trunk MCs are mesodermal in origin, while both neural crest and mesoderm populations contribute to cranial MCs. MCs appear to be recruited to specific vessels, such as the dorsal aorta in the trunk or the basilar artery in the head, and then migrate using inter-endothelial cell junctions as a scaffold to cover other vessels – preferentially the arteries. As well as providing important insights into MC behaviour, the tools developed here should serve as a valuable resource for the community for future analyses of vascular development.

Determining dendritic diversity in Drosophila

Neuronal morphology is highly variable, particularly in terms of the complexity of dendritic arborisation, and this variability is crucial for appropriate function. But how is such diversity established and regulated? Wesley Grueber and colleagues (p. 1351) set out to address the transcriptional inputs into this process using a subset of Drosophila sensory neurons, the multidendritic (md) neurons, whose morphology is regulated by the transcription factor Cut. Cut expression is absent in neurons that have simple morphology and function as proprioceptors, but is expressed at variable levels in nociceptive or touch-sensitive neurons with more complex dendrites. Through a series of mosaic genetic analyses, the authors find that Cut represses the expression of the Pdm1/2 transcription factors in a subset of md neurons, which suppresses the ability of Pdm1/2 to restrain dendritic arborisation. Upstream of Cut, the transcriptional repressors Vestigial and Scalloped modulate Cut levels to limit dendritic elaboration – in this case repressing a complex morphology and favouring a less complex type of branching. Together, these data identify a network of repressive interactions that regulate neuronal morphology and thus help to define neuronal identity and diversity.

PLUS…

CncRNAs: RNAs with both coding and non-coding roles in development

RNAs are known to regulate diverse biological processes, either as protein-encoding molecules or as non-coding RNAs. However, a third class that comprises RNAs endowed with both protein coding and non-coding functions has recently emerged. Such bi-functional ‘coding and non-coding RNAs’ (cncRNAs) have been shown to play important roles in distinct developmental processes in plants and animals. Here, Karuna Sampath and Anne Ephrussi discuss key examples of cncRNAs and review their roles, regulation and mechanisms of action during development. See the Primer on p. 1234

Developmental origin and lineage plasticity of endogenous cardiac stem cells

Over the past two decades, several populations of cardiac stem cells have been described in the adult mammalian heart. Here, Richard Harvey, Jason Kovacic and colleagues summarize what is known about different these populations, highlighting their developmental origins and defining characteristics, and their possible contribution to heart organogenesis and regeneration. See the Review on p. 1242

Lineage-specific stem cells, signals and asymmetries during stomatal development

Stomata – the dispersed pores found in the epidermis of land plants that facilitate gas exchange – are formed from progenitor cells that execute a series of differentiation events and stereotypical cell divisions. Here, Soon-Ki Han and Keiko Torii review the intrinsic and extrinsic factors that control stomatal development, highlighting striking similarities between plants and animals with regards to their mechanisms of specialized cell differentiation. See the Review on p. 1259

(2 votes)

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This interview first featured on Disease Models and Mechanisms.

Gerald (Gerry) Rubin, pioneer in Drosophila genetics, is Founding Director of the HHMI-funded Janelia Research Campus. In this interview, Gerry recounts key events and collaborations that have shaped his unique approach to scientific exploration, decision-making, management and mentorship – an approach that forms the cornerstone of the model adopted at Janelia to tackle problems in interdisciplinary biomedical research. Gerry describes his remarkable journey from newcomer to internationally renowned leader in the fly field, highlighting his contributions to the tools and resources that have helped establish Drosophila as an important model in translational research. Describing himself as a ‘tool builder’, his current focus is on developing approaches for in-depth study of the fly nervous system, in order to understand key principles in neurobiology. Gerry was interviewed by Ross Cagan, Senior Editor of Disease Models & Mechanisms.

Gerald M. Rubin was born in Boston, Massachusetts, in 1950. He undertook his undergraduate degree in Biology at MIT from 1967 to 1971, and worked at Cold Spring Harbor Laboratory during the summers of 1970 and 1971. For his PhD, he studied 5.8S ribosomal RNA under the supervision of Sydney Brenner at the MRC Laboratory of Molecular Biology, University of Cambridge. After graduating in 1974, Gerry undertook post-doctoral research in David Hogness’s lab at Stanford University. This marked Gerry’s first step into Drosophila research, which at that time was experiencing resurgence in the biomedical arena. Gerry’s first faculty appointment was at Harvard Medical School, but he moved after 4 years to the Carnegie Institute of Washington’s Department of Embryology. It was here that, together with Allan Spradling, Gerry pioneered the use of transposable elements as a tool for genetic manipulation – a breakthrough that revolutionized Drosophila genetics. In 1983, Gerry moved to the University of California, Berkeley, where his group studied pattern formation and signal transduction during development of the fly eye; he later led the sequencing of the fruit fly genome, which was completed in 2000. Currently, Gerry is a Vice President at Howard Hughes Medical Institute and the Executive Director of its biomedical research institute, the Janelia Research Campus in Ashburn, Virginia. His lab probes fly brains to gain insight into the neuronal circuits underlying learning and memory, sleep regulation, visual perception and sensory integration, and Gerry remains dedicated to the development of neurobiology and genomics tools. He has been honored with a long list of awards in recognition of his contributions to Drosophila research so far.

My first question is: how did you become interested in flies?

I was a graduate student in Cambridge, England, in the pre-cloning, pre-DNA-sequencing era, working on RNA sequencing in yeast. David Hogness came and gave a seminar in 1973 on his recent work on fly chromosomes. At that time, many labs, including his, were trying to develop methods for cloning segments of eukaryotic DNA in bacteria. Dave’s work really fascinated me and prompted me to apply to do my post-doctoral research in his lab. He agreed, and I was ready to move to Stanford in September 1974. By then, recombinant DNA technology was up and running, and the Hogness lab had generated about 200 Drosophila recombinant clones. My first project was to make a library that had enough clones in it to cover all the DNA sequences in the genome. This was the first of several times in my career when I was fortunate to be in the right place at the right time. There had been almost no prior work on cloned DNA segments, so almost any experiment led to novel insights. The experience also taught me the power of new techniques to advance science.

You and Allan Spradling pioneered the use of transposable P elements as a gene manipulation tool – this is one of the first things I learned about in Drosophila genetics. How did you come to be involved in this work?

Most of my post-doc time was spent characterizing the organization of fly DNA by making restriction maps of clones, measuring the amount of repetitive DNA (using reassociation kinetics – readers over the age of 50 will remember this technique!) and performing in situ hybridization to polytene chromosomes. We found a lot of repetitive DNA dispersed in the fly genome. Around the same time, Eric Davidson at Caltech had proposed that repetitive DNA segments might have important regulatory roles, so I continued studying them after setting up my own lab at Harvard. We soon realized that many of them were retroviral transposable elements and that they were causing spontaneous mutations in the genome. There was a growing body of literature on movable genetic elements, and Mel Green – among others – had proposed that their insertion caused some of the unstable mutations that had been described in Drosophila. We decided to try to clone the white locus – a gene that is important for eye color in Drosophila – because the many spontaneous mutations at this locus would allow us to directly test these ideas. In 1980, we succeeded in cloning the locus, by a method now known as transposon tagging, and we were soon able to show that several mutations in the white locus were in fact due to transposon insertion. That same year, I went to the Cold Spring Harbor symposium on transposable elements and heard Bill Engels give a talk on hybrid dysgenesis, which he proposed was caused by a family of transposons called P elements. In the slow lunch line following Engel’s talk, Margaret Kidwell, Paul Bingham and I designed an experiment to generate and molecularly characterize hybrid-dysgenesis-induced mutations in white. If Engel’s hypothesis were correct, the mutant whitegenes would contain insertions of the postulated P element. This turned out to be the case.

At Carnegie, I went on to characterize the structure of a large number of P elements. We discovered that there were full-length elements with a conserved structure, and a heterogeneous set of smaller elements containing internal deletions. This was immediately reminiscent of Barbara McClintock’s pioneering work in maize that defined ‘two-element systems’ of autonomously transposing and defective elements dependent on the autonomous elements for trans-acting functions. At that point it was obvious that the full-length P elements might be good vectors for making transgenic animals. Allan Spradling, my colleague at Carnegie, and I discussed trying to make this work. Allan took on the task of injecting embryos and I did most of the molecular work. It took us less than a year to have initial success and we reported our work in two articles in Science in the fall of 1982. We did all the experiments ourselves because it was a high-risk ‘nutty’ experiment!

The breakthrough dovetailed nicely with the burst of genetic screens that were happening around the same time. Did you know, when you were doing this work with Allan, the impact it would have?

We realized, from the work in yeast and bacteria, that the ability to make transgenic animals would be tremendously powerful. Methods to genetically engineer the genomes of single-cell organisms had been around for a while, but we were the first to successfully engineer the germline of a multicellular organism. A lot of people had been interested in doing this, and we were fortunate that the experiments we tried actually worked. A lot of things fell into place and it was remarkably efficient and successful. It was one of the few times you have in your career as a scientist when everything falls into place and the sort of dream experiment actually works the way you draw it up on paper. Once we had the system up and running, we passed on the reagents and so, by the time our paper was published, several other labs had already confirmed that it worked.

The P-element-based approach came along at a good time because everyone was hungry for positional cloning. Everyone had in mind the genes they wanted to identify and the experiments they wanted to do. There were a lot of fascinating developmental mutants, for example those isolated in the Nobel-Prize-winning genetic screens of Nüsslein-Volhard and Wieschaus, that hadn’t been characterized on a molecular level – we had no idea how the mutations were affecting cellular processes. The field then really took off and I think it was the synergy between molecular cloning and all the mutants and techniques that we already had that meant we could finally get at molecular mechanisms. A tremendous amount of data came out very quickly from many laboratories, particularly on developmental processes, and it was information that we hadn’t been able to glean using classical embryology in flies – or indeed any other organism. The majority of the components of all the signal transduction pathways that exist in humans were first discovered through this work. We could now ask questions that were just not possible to ask beforehand. It was as though the whole field awakened because of the sudden leap in several key technologies.

Your decision to share the reagents was critical. What made you decide to do this?

There is a tradition to share among Drosophila researchers, going back to the days of Thomas Morgan. The fly field has always seemed much more open in this respect than the mammalian field. Allan and I considered our options: we had this very useful technique and could wait until it was published to distribute it – which would give us exclusive access for 6-8 months – or to give it to people straight away. We decided that the benefits of distributing it immediately would outweigh any progress we could make in our work within a few months. I learned a lot from the experience and think it one of the better decisions I have made in my life. I consider myself to be a tool builder – the thing I’m most proud of in my scientific career is the development of tools and methods. Post-docs in my lab were eager to test hypotheses, but what has always motivated me is the building of tools that help overcome technical obstacles that block progress.

You led the fly genome project that was completed back in 2000. How did you get involved with that and what did the experience teach you?

My lab was doing interesting work on eye development at the time, and I took on the task of leading the genome project with some reluctance. Allan and I felt that the fly genome really needed to be sequenced, and we realized that we should take the lead because we were well-established and in the position to be doing something for the community. We got a grant and recruited some younger scientists, and I became the ‘figurehead’ of the project. Over time many of the younger scientists got bored or were hired by industry, and I needed to spend more and more of my time on the project. But I had staked my reputation that the project would be completed. So I was glad to be able to collaborate with Celera Genomics and Craig Venter, which was not only very enjoyable and a tremendous help in getting the project completed, but also demonstrated the power of the whole-genome shotgun method for sequencing large genomes. Once the fly sequence was available, I happily got out of the genome sequencing field and returned to the interesting questions that could now be asked about gene organization and function.

One important thing my genomics experience taught me was that I like management. I’m one of the few scientists that I know who actually enjoys management and thinks it is, in its own way, as interesting and challenging as scientific discovery and research. Managing projects, managing people, getting people to work well together and doing collaborative interdisciplinary research projects is a unique kind of challenge. This combination of enjoying scientific discovery as well as management naturally led me to my current role at Janelia.

Let’s talk a little bit about Janelia, which you have seen evolve from concept to implementation. What was the thinking behind its approach to interdisciplinary research, and what do you hope the long-term impact of the campus will be?

I feel that the way research is done in the US nowadays, where scientists depend for their livelihood on getting their grants renewed, can have a profound negative effect on research. It can make the work short-sighted by forcing scientists to pursue directions depending on what the funding agencies want, rather than by following their instincts and passions. I have always felt that this isn’t the ideal way to do all science. I moved to Janelia at a time when collaborative research and tool building were also undervalued and underappreciated. If someone wanted to build a new optical microscope, physics departments wouldn’t hire them because optics is old physics, and they wanted string theorists. In biology, people cared only about the hypothesis being tested and not about the tools. The tools are needed to advance science, yet science wasn’t – and still isn’t – funded to align well with this. There is a lack of appreciation for basic research in general, although basic science brings the fundamental breakthroughs that underlie translational research. Just look at CRISPR/Cas9, which would never have emerged if we didn’t have people studying ‘weird’ phenomena in bacteria. The pressure for recipients of grants to show short-term return on investment by tackling ‘practical’ problems – often defined top-down by funding agencies – is something I have seen steadily increase during my 40 years in science.

I felt that places like the MRC Laboratory of Molecular Biology [LMB], where I was fortunate enough to do my PhD, had a much higher rate of innovative research. I began to think about what made such places so great. As they were internally funded, people didn’t worry about convincing grant review committees to fund their research. Decisions got made much more quickly, the labs were small and people didn’t have other responsibilities; they could keep working in the lab, even at a late stage in their career. At the MRC LMB, I would see Nobel Prize winners with a pipette in hand, doing experiments 8 hours a day, 5 days a week. You would never see that in the US, and I had a rude awakening when I came back here.

I wanted to create a supportive environment for aspiring scientists who really wanted to just keep doing science without having to manage an enterprise and raise funds. And where there would be a strong synergy between the work in individual labs. I think Janelia provides that kind of environment. It’s not right for everyone – maybe it’s only right for 5% of scientists – but for those people it provides something very special that would be difficult to find elsewhere. My short-term goal is to help all the talented people we have recruited to be successful in doing important, innovative science that would be unlikely to happen elsewhere. My ultimate goal is to have a disruptive impact on scientific culture as a whole, and to change the way a significant fraction of research is funded and scientists are evaluated, especially in the US, by demonstrating the success of an alternative model. I look at Janelia as an experiment in the sociology of science and we continue to refine our working hypothesis. But I think the initial data from our first 10 years are very encouraging.

What would you say to a young scientist thinking about entering the fly field, particularly in terms of the place of Drosophila in this brave new world of translational research?

I think there’s no denying that Drosophila has been very useful as a disease model. Many components of signal transduction pathways, which are important drug targets, were discovered in yeast, worms or flies. People are working on very interesting experiments relating to growth control, cell movement and other basic mechanisms that are important in disease contexts. Drawing from my own scientific interests, I think there is a lot that flies can contribute to neurobiology. Flies show complex behavior, and I believe that the basic rules about how a biologically constructed computational device can perceive the world, navigate through it, learn and remember things, can be learned by studying flies. Flies are particularly amenable to a ‘black box approach’ in science: studying the consequences of manipulating genes and cells using clever assays can yield information that doesn’t depend on having a good hypothesis. You can gather information, in a non-biased way, on how things work.

From an intellectual point of view, I think that working on an organism like Drosophila is highly rewarding. Certainly for students, the ability to design and do really interesting experiments and see the outcome in a reasonable timeframe is tremendously powerful in terms of learning how to do science. In other fields, experiments can move so slowly that if you’re a graduate student you don’t really get to do much during the limited time you have for your PhD. The difficulty lies in convincing the funding agencies of the value of model systems such as Drosophila. There is insufficient appreciation from people making these decisions, most of who have worked in medicine or using mammalian systems, about the power of a simpler model. The work going on in vertebrate systems is important, but I think that the simpler systems deserve more investment than they get at present. Dollar for dollar the fly community has produced more insights with medical relevance than the mouse community. Similarly, in the cancer field, most of the important cell cycle mutants and checkpoints initially came from studies in yeast. The intellectual history, the source of important ideas and breakthroughs, isn’t always fully appreciated, and thus the contribution of simple systems is undervalued.

You’ve mentioned in the past that one of your biggest achievements in science is the people you have trained. Certainly, as somebody on the outside looking in, you’ve had an astonishing number of amazing post-docs that have gone on to make an impact. What is your approach to training?

It’s true that this is one of the things I’m most proud of. It certainly is as rewarding as a good publication record, and of course it’s a two-way street. The fact that I had all those great people in my lab made it easy for me to develop my own reputation based on the work they did.

I was fortunate as a graduate student; I pretty much worked on my own. I never wanted anyone telling me what to do. I was the sole author of two of the three papers I published as a graduate student; on the other one I had a co-author but it wasn’t my adviser. I had my own project and it moved in the direction I chose. I think most people are more motivated when they’re working on their idea and not an idea that someone else gives them. I was also fortunate because I entered a field that was in its early stages. The Drosophila community was growing and there weren’t that many labs who had established research programs using recombinant DNA and so I attracted to my lab a remarkable group of highly talented people. I realized that the way I would get the most out of them was to let them work on a problem they were passionate about, tell them they could take that problem with them when they left my lab, and just be on hand to provide technical advice and to act as a sounding board for ideas or help with writing manuscripts. Smart people want to be in an environment where they have freedom to explore their ideas and are challenged by other smart people. It was wonderful for me because every day there was interesting science going on, and I never felt like I needed to be the source of all the ideas or that everything was on my shoulders. I was creating an environment that facilitated other people’s ability to work, rather than directing them. As a young scientist, I was always in an environment that was positive, upbeat and optimistic. I feel tremendously fortunate and feel that I have a big obligation to try and recreate some of that for the next generation.

What advice would you give to a young start-up on how to run a successful lab?

Keep it small and be highly selective. This advice seems counterintuitive: you’re thinking, you have an empty lab, that you have some money to hire people and any reasonable pair of hands is better than nothing. But actually, if you get the wrong person, it can be disastrous. Aim to hire people smarter or more talented than yourself. Having people who are not motivated and passionate can be very detrimental – motivation and passion are probably as important as intellectual ability. Also, you should protect your time so that you can continue to do things yourself at the bench.

Finally, if not science, what would you be doing?

I got my first job working in a lab when I was 14 years old (washing glassware) and I knew right from that point that I wanted to work in science. I suppose if I hadn’t gotten a faculty job I would be teaching high-school biology. As I’ve mentioned, I’ve been extremely fortunate in every stage of my career. I’ve been in the right place at the right time on several occasions and I got tremendous support from my advisers and teachers – as well as from my wife of 38 years. My graduate and post-doc experiences were also extremely positive. I can’t imagine anything else I could have done that would have been as satisfying or as much fun – I never looked at it as work. I’m always amazed that I get paid for doing what I love doing.

(8 votes)

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Surrounded by the breathtaking landscape of the Rocky Mountains, hundreds of graduate students and researchers gathered for the 8^th biennial Canadian Developmental Biology Conference at the Banff Centre, minutes outside of Banff, Alberta. This four-day conference was filled with a variety of stimulating seminars and poster sessions, reflecting some of the latest advances in the field of developmental biology; meanwhile the easy-going conference atmosphere encouraged a number of friendly and thought-provoking discussions between students, post-docs, and scientists from across Canada and abroad.

Researchers from diverse backgrounds presented in the meeting’s five main scientific sessions, incorporating a number of model organism systems and developmental processes.  The first session – stem cells and regeneration – included a talk from Jeff Biernaskie (University of Calgary) on the application of adult dermal stem cells to promote wound-healing after skin grafts, using a mouse xenograft model. The session also included a talk from Rohan Khadilkar (University of British Columbia), who received the award for the best post-doctoral presentation on his research on the Drosophila hematopoietic stem cell niche and the role of septate junctions in moderating HSC differentiation. The second session focused on gene expression and development. Julie Claycomb (University of Toronto) presented on the role of an Argonaute protein, CSR-1, in licensing C. elegans germline gene expression through small RNAs and chromatin modifications. Other talks were Marie Kmita’s (University of Montréal) exploration of a Hoxa11 antisense enhancer to regulate distal limb development, and Alexandra Dallaire’s (Best student talk winner, CHU de Québec Research Centre) discussion of how microRNAs mediate mRNA stability in C. elegans.

Following were sessions on growth, differentiation and patterning – including a talk from Dominique Bergmann (Stanford University) on asymmetric cell division and fate specification in plant stomatal cells – as well as cell proliferation, migration and morphogenesis. The latter, featured, amongst others, a presentation by Vanessa Auld (University of British Columbia) on glia-ECM interactions in Drosophila and their role in protecting the peripheral nervous system. The fifth and final session focused on developmental models of disease. One of the highlights from this session was a talk by Brian Ciruna (Princeton University) on a zebrafish ciliary-defect model of scoliosis.

In addition to the five primary sessions, a major highlight was the keynote lecture and conference education session. Keynote speaker Freda Miller (University of Toronto), gave a captivating presentation on the use of the mouse cerebral cortex to study neurogenesis and the role of translational repression in regulating neuronal cell fates. This lecture was a wonderful way to start the conference and sparked many interesting discussions during the night’s opening reception. Furthermore, all attendees enjoyed an interactive presentation by Scott Barolo (University of Michigan), who demonstrated how the game Mastermind could be used to teach scientific thinking strategies.

On the final evening of the conference, attendees donned their cowboy boots and Western attire and headed over to MountainView Barbeque for a buffet-style meal and lively night of socializing. The barbeque was complete with a huge bonfire and live country music band, and to led hours of cheerful conversation and even some line-dancing.

This year’s conference provided an excellent opportunity for Canadian and international biologists from all career stages to interact and discuss leading findings in developmental biology research. On behalf of all conference attendees, I would like to say a tremendous thank you to the conference organizers, Savraj Grewal, Dave Hansen and Sarah McFarlane (University of Calgary), for putting together an excellent program of speakers and events, including the poster sessions, 60-second science presentations and conference banquet. Also to Paul Mains for organizing the judging of trainee poster presentations, and to the meeting sponsors (CIHR, SDB and many others). Congratulations to all the winners of the poster competition (below) and the Society of Developmental Biology travel and financial awards. Namely, Rohan Khadilkar for the best postdoctoral talk (SDB cash award), and Alexandra Dallaire (SDB travel award) and Anna Kobb (SDB cash award) for the best graduate student talks.

The 9^th Canadian Developmental Biology conference will be held in 2018 in Mont-Tremblant, Québec. Looking forward to seeing you all there!

By: Isabella Skuplik

Student poster award winners: Aarya Chithran, Miranda Hunter, Katharine Goodwin, Rotem Lavy, Enrique Gamero-Estevez, Adam Kramer, Tanya Foley, Corey Arnold, Sonya Widen, Eric Hall, Raghda Gemae, Mriga Das, Victoria Yan, Isabella Skuplik, Bensun Fong, Dova Brenman.

Postdoctoral poster award winners: Matthew Hildebrandt, Pierre Mattar, and Sérgio Simões (SDB cash awards), Guang Yang (SDB travel award).

Travel award winners: Sarah Garner, Siavash Amon, Amanda Baumholtz, Scott De Vito, Adrienne Elbert, Sarah Gignac, Zachary Hall, Adam Kramer, Stephanie Tkachuk, Jessica Yu.

Elk passing through the Banff Centre campus

(9 votes)

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Valeria Yartseva was the winner of last year’s Society for Developmental Biology (SDB) meeting poster competition. Her prize was to attend the spring meeting of the British Society for Developmental Biology (BSDB), held jointly with the British Society for Cell Biology at the University of Warwick in the UK. Continuing the interview chain, Valeria interviewed Mathew Tata, who won the poster prize at the meeting. Matthew’s prize will be to attend the SDB meeting in Boston, USA, in the summer.

VY: Congratulations on winning the BSDB poster prize Mathew.

MT: Thank you very much!

VY: Can you tell us a little about your lab?
MT: I work in the lab of Professor Christiana Ruhrberg at the Institute of Ophthalmology, at University College London, in the UK. As a lab we work on the development and disease of blood vessel growth. In particular, I work on the development of the mammalian brain. I want to understand how brain vessels are involved in brain development and how they may contribute extrinsic signals.

VY: How long have you been in this lab?

MT: Too long! I have overstayed my welcome and have been there for 4 years now.

VY: That is actually quite short for the States. That is considered being an over-achiever!

MT: Yes, I guess it is quite normal.

VY: Could you briefly tell us what your poster is about?

My poster is about how the vasculature is important in stemness within the mammalian CNS. The interaction between blood vessels and Vascular Endothelial Growth Factor with stem cells in the adult has been well characterised.  However, very little is known about their role in the embryo. I wanted to know whether there was any correlation between the blood vessels and neural development in the embryo, and specifically the effect of blood vessels in embryonic neuroprogenitor cells. I showed that there was a spatiotemporal correlation between embryonic neurogenesis and blood vessel growth. In addition, I discovered that if you take away blood vessel growth in the embryonic hindbrain using mouse mutant models, neuroprogenitor cells rapidly exit the cell cycle and terminally differentiate, and this impairs the growth of that area of the nervous system.  We haven’t yet identified the candidate niche molecule, but we have a few ideas.

VY: That sounds really fascinating. What is the single experiment that you are most proud of?

MT: They have all been equally painful! I would say that the first time I actually observed neuroprogenitor cell processes interacting with vessels was very exciting.  Everything I had seen up until then was highly ambiguous, so it was nice to confirm that I was in the right area and was looking at the problem from the right perspective. There is still much to be learnt about it though!

VY: Have you won a poster prize at a meeting before?

MT: I only won one at my university, but that was a small affair, nothing at this scale. So I am a bit humbled.

VY: What is next for you?

MT: That is the 10 billion dollar question! I am still very much in love with research and I really enjoy being at the bench. But there are other things that interest me as well, like communication and I especially enjoy teaching. At the moment I am just enjoying pursuing my thesis and trying to get a paper out (as the old story goes). I think I will be looking at postdocs for sure.

VY: And will you be attending the SDB meeting later this year?

MT: Absolutely!

VY: Thank you so much, this has been a pleasure!

MT: Thank you!

(9 votes)

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8th Young Embryologist Network Conference

27th May 2016

09:15-18.00 UCL Institute of Child Health

Registration and abstract submission are now open!

The 8th Young Embryologist Network Conference aims to bring together developmental biologists from across the UK (and beyond) to discuss their work.

This year, YEN is honoured to have Professor Paul Martin from the University of Bristol present The Sammy Lee Memorial Lecture. As well as three talk sessions and a poster break, we will also have imaging session to discuss the latest advances in microscopy and live imaging techniques. Additionally, we have included a novel session to discuss the recent development over human and mouse embryology that will be presented by Dr Srinivas (University of Oxford) and Dr Niakan (The Francis Crick Institute).

As in previous years, this meeting is completely free thanks to the generosity of our sponsors: The Company of Biologists, New England Biolabs, REGEN, F1000, Cambridge Bioscience, Promega and UCL Institute of Child Health.

We are looking for talks and posters from PhD students and Post-docs on Evo-Devo, Stem Cell and Developmental Biology

The deadline for abstract submission is Midnight 5th of May 2016.

For more information go to our website!

(2 votes)

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What is Bento Lab?

Bento Lab is a minimal molecular biology laboratory, containing the essentials tools for genetic analysis. There’s a centrifuge, a PCR thermocycler to copy DNA, and a system for gel electrophoresis, to visualise DNA.

How was the idea of Bento Lab born?

Bento Lab was born out of a series of workshops and projects that my co-founder Bethan and I undertook since 2012. We were very interested in exploring how different groups outside of academia and industry interacted with emerging biosciences, groups such as artists and designers, parents and teachers, and hobby scientists. In particular, we were fascinated by the maker community, a growing network of enthusiasts engaging with electronics, computing and other technologies as a hobby. In molecular biology, a small but growing community of Do-it-yourself biologists was emerging, analogous to the maker community. We thought this was very interesting and could potentially play a really interesting role of fostering hands-on literacy for topics like genetics.

But we noticed quickly, that the community was still in its infancy. There were many interesting open hardware projects, but for many newcomers the lack of guidance could be a bit frustrating. Seemingly every week, emails would be sent to the mailing list asking how to get started. Because there were no easy to use and affordable starter tools, for many their initial spark of interest didn’t turn into a longer-term hobby. Bethan and I saw a real need for an infrastructure for engaging with molecular biology as an ambitious beginner, something that could accompany you on the journey from someone with an interest to a seasoned citizen scientist or even a professional. We saw that these things existed in other communities, for example with Arduino in electronics. This is what we had in mind for Bento Lab.

Kickstarter and beyond

Of course, we are only at the beginning. What’s very exciting is that we got such an overwhelming amount of support for our Kickstarter campaign. For the past 6 months we have beta-tested Bento Lab devices with users from all around the world, and we are very excited to work with all of our Kickstarter supporters in the coming months and see their projects come to life.

We’ve also designed a Starter Kit for Bento Lab with experiments designed for learning all the basic procedures, how to interpret results, how to ask for help, how to be a responsible scientist – all those aspects. With this project, we don’t just want to build an easy-to-use laboratory, but foster a community.

Although we reached our target for funding on Kickstarter, we have two more exciting stretch goals that we’re moving towards. We’ve been approached by many schools and teachers about using Bento Lab in the classroom and this is really exciting for us. If we reach £150,000 in funding, we can fund a pilot programme to work with teachers, education organisations and academic partners to create teaching materials for hands-on genetics in the classroom. Personally, I think this could be really significant and I would have loved to have done practical genetics experiments when I was in school.

If you know of anyone who you think we should talk to for the Bento Lab project in general or the educational pilot in particular, please get in touch, we’d love to hear from you.

(18 votes)

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Here you can find out more about our video protocol on using light sheet microscopy to image zebrafish eye development.

Light sheet fluorescence microscopy has quickly become a popular technique in developmental biology. This method is very gentle to the samples, with fast acquisition speed and allows capturing the samples from any angle or from multiple angles at the same time (so called multi view imaging) (Stelzer, 2015). Such multi view imaging overcomes the degradation of the signal in Z axis and allows imaging of large specimens with high and almost isotropic resolution. The fact that light sheet microscopy is trending was confirmed when it was voted the method of the year 2014 by Nature Methods.

The major obstacle to mainstream adoption of this method was until recently the technical complexity for many biologists without a background in optics and computer science (Reynaud et al., 2015). The good news is that things have started to change and performing successful light sheet experiments is getting easier. For some time now, there are commercially available light sheet microscopes, which are easy to operate and the software solutions are not lagging behind, with plugins to process the resulting datasets as clickable GUIs (Amat et al., 2015; Preibisch et al., 2014; Preibisch et al., 2010) or Zeiss own solution in ZEN software. One word of warning, your hardware still has to be prepared to handle large volumes of data.

We recently contributed a video protocol (Icha, Schmied et al., 2016) to document a versatile light sheet microscopy experimental pipeline using a commercial microscope and an open source software solution for data processing. Specifically, we used the Lightsheet Z.1 microscope from Zeiss and the Multiview reconstruction application in Fiji to process the data. We demonstrated our approach by imaging several stages of retinal development in zebrafish. The general application for our pipeline would be long-term time-lapse imaging of morphogenetic processes during development using single or multi view acquisition. The protocol will take you through the essential steps of a light sheet microscopy experiment from mounting the sample to processing the data. The most complicated step is not taking the images, but the subsequent combination of image information from multiple views together. The solution we use is embedding fluorescent beads around the sample to register the different views onto each other and thereby to reconstruct the imaged volume of the sample.

In the associated text, you will find a step-by-step protocol including all the experimental details plus troubleshooting in the discussion section. This should be especially useful for the newcomers to the light sheet fluorescence microscopy field.

This video protocol was created as a collaboration between the Norden lab (twitter @NordenLab) and the Tomancak lab (twitter @PavelTomancak) at MPI-CBG in Dresden. Enjoy and don’t hesitate to contact us in case you have questions. The full video is also available on the Norden lab website.

Other useful links:

EMBO course in Light sheet microscopy 2016

SPIM – Light Sheet Microscopy Literature Database

Open source hardware: DIY light sheet microscopes

Open SPIM wiki page

Open SPIN microscopy

Nature Methods method of the year 2014 thematic issue

References:

Amat, F., Höckendorf, B., Wan, Y., Lemon, W. C., McDole, K. and Keller, P. J. (2015). Efficient processing and analysis of large-scale light-sheet microscopy data. Nat Protoc 10, 1679–1696.

Icha, J., Schmied, C., Sidhaye, J., Tomancak, P., Preibisch, S., Norden, C. (2016). Using Light Sheet Fluorescence Microscopy to Image Zebrafish Eye Development. J Vis Exp 110, e53966.

Preibisch, S., Amat, F., Stamataki, E., Sarov, M., Singer, R. H., Myers, E. and Tomancak, P. (2014). Efficient Bayesian-based multiview deconvolution. Nat Meth 11, 645–648.

Preibisch, S., Saalfeld, S., Schindelin, J. and Tomancak, P. (2010). Software for bead-based registration of selective plane illumination microscopy data. Nat Meth 7, 418–419.

Reynaud, E. G., Peychl, J., Huisken, J. and Tomancak, P. (2015). Guide to light-sheet microscopy for adventurous biologists. Nat Meth 12, 30–34.

Stelzer, E. H. K. (2015). Light-sheet fluorescence microscopy for quantitative biology. Nat Meth 12, 23–26.

(4 votes)

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Enrico Coen: winner of the 2016 BSDB Waddington Medal

The Cheryll Tickle Medal revealed

Elena Scarpa: the BSDB Beddington Medal winner

Summary of all BSCB/BSDB awards

(1 votes)

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The Novo Nordisk Foundation Section for Basic Stem Cell Biology, Danish Stem Cell Center, Faculty of Health and Medical Sciences University of Copenhagen

The University seeks to appoint three Group Leaders in Pancreatic Cancer, Stem Cell Biology and Bioengineering to The Novo Nordisk Foundation Section for Basic Stem Cell Biology (BasicStem) at the Danish Stem Cell Center (DanStem) to commence as soon as possible. The positions are for six years with possible extensions depending on the outcome of a peer reviews.

Background

The Danish Stem Cell Center (DanStem) is an international research center at the University of Copenhagen. The overall scientific goal is to develop new stem cell-based therapeutic approaches, currently in the area of diabetes and cancer addressing basic questions in stem cell and developmental biology and seeking to identify the factors that govern the development of different cell types in the body. Read about DanStem at www.danstem.ku.dk/.

Group Leader in Pancreatic Cancer

Particular interest in basic and disease-oriented pancreatic cancer biology

Group Leader in Stem Cell Biology

Particular interest in addressing fundamental questions in stem cell biology by using single cell behaviour analysis

Group Leader in Bioengineering

Particular interest in addressing fundamental questions in stem cell biology using bioengineering approaches. Experience with materials science and/or devices (e.g. microfluids) would be an advantage.

The Group Leaders duties will primarily consist of:

• Developing a strong research program.
• The Group Leaders must be willing to synergize with other DanStem scientists and contribute to common activities at DanStem such as seminars and PhD courses.
• The Group Leaders are expected to take full responsibility for training and supervision of young researchers, for management of each of their own group, and for publication/dissemination of research results.
• The Group Leaders are expected to actively contribute to teaching activities and education activities
• Academic assessments

The closing date for applications is 23.59 pm, May 1st, 2016

Apply online: http://employment.ku.dk/all-vacancies/?show=795295

Only online applications will be accepted.

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