The following editorial by Nipam Patel appears in Development issue 139(15). The corresponding Featured Topic on Evolutionary Crossroads in Developmental Biology includes all the primer articles mentioned and linked in the editorial.

Currently, most developmental biologists work on one or more of a relatively small number of experimental systems, such as Arabidopsis thaliana, Drosophila melanogaster (fruit fly), Xenopus laevis (frog), Caenorhabditis elegans (nematode), Danio rerio (zebrafish) and Mus musculus (mouse), and their research is largely focused on understanding developmental mechanisms at the genetic, biochemical and molecular levels. This bias toward certain species is easily understood – analyses in these organisms is greatly facilitated by the availability of an array of genetic, molecular and genomic resources that have been generated over the years by large communities of scientists. However, the field of developmental biology has a long and colourful history of experimentation with a remarkably varied assemblage of creatures, and many crucial discoveries were first made in species that are now relatively understudied. Furthermore, some species possess certain remarkable attributes that have generated interest for a very long time. For example, the axolotl (Ambystoma mexicanum, a Mexican salamander) is considered to be the champion of regeneration among vertebrates, and although the number of people working with axolotls is relatively small, they remain a species of great interest because of the potential breakthroughs that might come from them.

Another important reason that some developmental biologists have maintained interests in animals, plants and fungi outside of the main experimental systems comes from a desire to understand the evolution of development. Most of our model species are evolutionarily distant from one another, and in some cases certain aspects of their development are derived with respect to other closely related species. For example, the study of segmentation in Drosophila melanogaster has produced a multitude of remarkable insights into basic developmental mechanisms, but many of the well-understood steps in early patterning are atypical of the process of segmentation in arthropods as a whole. For this reason, developmental biologists have studied other arthropods, such as mosquitoes, beetles, crickets, grasshoppers, centipedes and spiders, to understand the diversity of developmental mechanisms at work in the process of segmentation. When placed into a phylogenetic framework, such comparative studies can also provide us with hypotheses as to how the process of segmentation has evolved within the arthropods and give us better insight into how segmentation is related between phyla.

The interest in such comparative studies and their implications stretches back through the entire history of developmental biology. The important evolutionary insight that they provide has long been recognised; Charles Darwin even devotes an entire chapter of The Origin of Species to a discussion of how development can help unravel the pattern and process of evolution. In more recent decades, genetics has proven to be a key bridge between developmental and evolutionary biologists. Although developmental and evolutionary geneticists often seem to speak very different languages, there is an increasing awareness of what one can contribute to the other, and a synthesis between the two has begun to yield remarkable insights in many cases. Furthermore, the ability to work with an increasing diversity of species has received a major boost owing to several technical breakthroughs. These include the genomic tools that allow us to quickly compare the genes that are shared and not shared between species, techniques such as in situ hybridisation, microarrays and transcriptome sequencing that facilitate comparative studies of the timing and pattern of gene expression and, finally, new tools for functional analyses that take advantage of breakthroughs in RNAi and transgenic technology.

For these reasons, research into the development of many species outside of the major experimental systems has flourished in recent years. Some, such as sea urchins, have indeed been studied for a very long time and can arguably now be placed in the pantheon of major ‘model’ systems. Their phylogenetic position as a sister group to the chordates provides insights into deuterostome origins, but at the same time they have made many direct contributions to our understanding of developmental mechanisms outside of any evolutionary context. Others, such as the cnidarian Nematostella, have risen to prominence relatively recently.

Starting about two years ago, Development began to publish a series of Primer articles under the banner ‘Evolutionary crossroads in developmental biology’, which aimed to review advances that have come from particular organisms, or closely related groups of organisms, that lie outside of the major experimental systems. Ten of these Primers have been published so far, and the organisms covered include Dictyostelium discoideum [slime mold (Schaap, 2011)], Cnidaria [including both Hydra and Nematostella (Technau and Steele, 2011)], cyclostomes [lamprey and hagfish (Shimeld and Donoghue, 2012)], tunicates (Lemaire, 2011), sea urchins (McClay, 2011), Physcomitrella patens [moss (Prigge and Bezanilla, 2010)], amphioxus (Bertrand and Escriva, 2011), annelids [including Platynereis, leech and Capitella (Ferrier, 2012)], spiders (Hilbrant et al., 2012) and hemichordates [including the acorn worm Saccoglossus kowalevskii (Röttinger and Lowe, 2012)]. Each Primer provides an overview of the phylogenetic position of the species, the experimental tools and techniques that are available for studying these organisms, and the evolutionary questions that can be addressed using this organism. It is important to remember that none of these are living ancestors, although some are thought to retain particularly striking ancestral features. For example, present day amphioxus is not the ancestor to all chordates, but it can be well argued that its genome has retained many ancestral features. Nevertheless, when placed into a phylogenetic context, each of the species discussed in these Primers can be used to make deductions about various common ancestors that did once exist. In so doing, this gives us insights into macroevolutionary processes that have shaped animal, plant and fungal diversity. Each article also highlights the usefulness of each species from a purely developmental perspective, and illustrates the impressive progress that can be made by relatively small communities of researchers applying modern tools.

Our world depends on maintaining biodiversity for its survival and, in a similar vein, the field of developmental biology is also strengthened by maintaining a wide diversity of experimental systems, each with its own unique and fascinating biology and place within the tree of life. This set of Primer articles is likely to expand as other non-model organisms are studied and developed, and will hopefully prove useful to those with a broad perspective on what it means to be a developmental biologist.

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Mae West was no biologist when she told us all that “Too much of a good thing can be wonderful.”  I shudder to think how little development would take place if any one cell type was produced in large amounts.  Thankfully, stem cells and those involved in tissue regeneration understand the importance of moderation. Today’s image is from a recent Development paper showing how Fox1/4 proteins restrict certain cell fates in lung epithelium, both during development and tissue regeneration.

The epithelial layer in our lungs is made of several cell types, including secretory Clara cells, ciliated epithelial cells, neuroendocrine cells, and large goblet cells.  During irritation or injury, such as pollution or cigarette smoke, goblet cells increase the production of mucus.  Only a few goblet cells are typically found in healthy lungs, but asthma or COPD (chronic obstructive pulmonary disease) patients have an increased number of goblet cells.  A recent Development paper describes the role of the transcription factors Fox1 and Fox4 in regulating the cell fate decisions that produce goblet cells during development and tissue regeneration.  Specifically, Li and colleagues found that Fox1/4 restricted the goblet cell lineage program by repressing disulfide isomerase anterior gradient 2, Agr2.  In addition, Li and colleagues found that Fox1/4 deletion caused a catastrophic loss of tissue regeneration, by driving differentiation of all secretory cells into the goblet cell lineage program.  The images above show lung tissue after chemical injury by naphthalene, which causes a rapid loss of Clara secretory epithelial cells from the airways.  Control tissue (left column) regenerated by day 20.  Without Fox1/4 (right column), tissue regeneration was defective, as seen as the presence of too many goblet cells (top row, arrows) and the lack of ciliated epithelial cells (β tubulin IV in red, bottom row).

For a more general description of this image, see my imaging blog within EuroStemCell, the European stem cell portal.

Li S, Wang Y, Zhang Y, Lu MM, Demayo FJ, Dekker JD, Tucker PW, & Morrisey EE (2012). Foxp1/4 control epithelial cell fate during lung development and regeneration through regulation of anterior gradient 2. Development (Cambridge, England), 139 (14), 2500-9 PMID: 22675208

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Here are the research highlights from the current issue from Development:

Cxcr4a sets proliferative response to Hh

The Hedgehog (Hh) pathway controls both patterning and proliferation during development, but how do embryonic cells distinguish between these activities? On p. 2711, Pia Aanstad and colleagues provide data that indicates that proliferative responses to Hh signalling are context dependent. The researchers show that activation of Hh signalling promotes endodermal cell proliferation in zebrafish gastrula stage embryos but inhibits proliferation in neighbouring non-endodermal cells. Expression of the chemokine receptor Cxcr4a in gastrula stage endoderm determines the proliferative response to Hh signalling, they report, but does not affect the expression of Hh target genes involved in patterning. Finally, they show that Cxcr4a inhibits the activity of cAMP-dependent protein kinase A (a negative regulator of Hh signalling), and propose that Cxcr4a enhances Hh-dependent proliferation by promoting the activity of Gli. Together, these results indicate that Cxcr4a is required for Hh-dependent cell proliferation but not for Hh-dependent patterning. Thus, parallel activation of Cxcr4a might enable Hh signalling to control both patterning and proliferation during development.

Hh maintains testis somatic stem cells

Stem cells are specified and maintained by specific microenvironments called niches. In the Drosophila testis, somatic cyst stem cells (CySCs) give rise to cyst cells, which ensheath the differentiating germline stem cells (GSCs). Both stem cell pools are arranged around a group of somatic cells – the hub – that produce niche signals for both lineages. Now, Christian Bökel and co-workers report that CySC but not GSC maintenance requires Hedgehog (Hh) signalling in addition to Jak/Stat pathway activation (see p. 2663). The researchers report that CySCs unable to transduce the Hh signal are lost through differentiation, whereas Hh pathway overactivation in CySCs increases their proliferation. The additional cells generated by excessive Hh signalling remain confined to the testis tip and retain the ability to differentiate. Because Hh signalling also controls somatic cell populations in the fly ovary and the mammalian testis, these new observations reveal a greater organisational similarity between the somatic components of gonads across the sexes and phyla than previously appreciated.

ncRNAs keep genes silent

Noncoding RNAs (ncRNAs) help to establish transcriptional gene silencing during development by interacting with DNA and chromatin-modifying enzymes. But do they also help to maintain gene silencing? Here (p. 2792), Chandrasekhar Kanduri and colleagues explore the involvement of the Kcnq1ot1 ncRNA in the maintenance of gene silencing at the Kcnq1 imprinted domain in the mouse embryo. The Kcnq1 domain contains ubiquitously imprinted genes (UIGs), which show imprinted silencing in placental and embryonic tissues; placental-specific imprinted genes (PIGs), which are silenced on the paternal chromosome in the placenta only; and several non-imprinted genes (NIGs). By conditionally deleting the Kcnq1ot1 ncRNA at different stages of mouse development, the researchers show that this ncRNA is required to maintain UIG silencing throughout development, whereas silencing of some PIGs is maintained independently of Kcnq1ot1 ncRNA. Intriguingly, the researchers identify enhancer-specific histone modifications associated with actively transcribed NIGs. These, they propose, may limit the spread of ncRNA-mediated silencing. Together, these results suggest how ncRNAs might maintain transcriptional silencing in a spatiotemporal manner.

In vivo activities of miRNAs revealed

Hundreds of microRNAs (miRNAs) – short RNAs that mediate networks of post-transcriptional gene regulation – have been recorded in animals. Because cell-based assays and bioinformatics provide evidence for large numbers of functional targets for individual miRNAs, it is not obvious that manipulation of miRNAs will lead to interpretable phenotypes at the organismal level. However, on p. 2821, Eric Lai and co-workers describe a genome-wide transgenic resource for the conditional expression of Drosophila miRNAs and, surprisingly, report that the majority of the miRNA transgenes in their collection induce relatively specific mutant phenotypes when expressed in the developing wing. Many of these phenotypes resemble those produced by alterations in signalling and patterning genes and, notably, their specificities were not predictable from computational studies, thereby highlighting the usefulness of in vivo phenotypic assays of miRNA activity. Finally, the unexpectedly broad capacity of different miRNAs to generate specific dominant phenotypes in flies suggests that gain-of-function of diverse mammalian miRNAs may also generate an array of specific disease conditions.

A rib-tickling Hox10 motif

During the development of the vertebrate axial skeleton, Hox genes belonging to paralog group 10 play a role in blocking rib formation in the lumbar region of the vertebral column. Here (p. 2703), Moisés Mallo and colleagues investigate the molecular basis of the rib-repressing function of Hox10 proteins. The researchers identify two conserved motifs (M1 and M2) that flank the homeodomain of Hox10 proteins and show that M1, which is located next to the homeodomain’s N-terminal end, is required for Hox10 rib-repressing activity in mice. M1 contains two potential phosphorylation sites, they report, mutation of which to alanines results in a total loss of the rib-repressing properties of Hox10 proteins. Other experiments suggest that the activity of M1 requires interactions with more N-terminal parts of Hox10 and that M1 might also regulate Hox10 activity by altering the protein’s DNA-binding affinity through changes in the phosphorylation state of two conserved tyrosines in the homeodomain. Together, these results provide new insights into the regulation of rib development by Hox10 proteins.

Modelling EGFR patterning of fly epithelium

Epidermal growth factor receptor (EGFR) signalling regulates numerous processes throughout Drosophila development. For example, during oogenesis, an EGFR activation gradient induced by Gurken (a TGFα-like ligand secreted from the oocyte) patterns the follicular epithelium. On p. 2814, Stanislav Shvartsman and colleagues present a revised mathematical model for this important process, which initiates the formation of two dorsal eggshell appendages. Each of these appendages is derived from a primordium that comprises a patch of cells expressing the transcription factor gene broad (br) and an adjacent strip of cells expressing rhomboid (rho), which encodes a protease in the EGFR pathway. Previous models of eggshell patterning have not fully accounted for the coordinated expression of br and rho. The new model, however, proposes that the sequential action of feed-forward loops and Notch-mediated juxtacrine signals activated by the EGFR signalling gradient establishes rho expression, successfully describes the wild-type br and rho expression patterns, and accounts for changes in these patterns in response to genetic perturbations.

Plus…

Toward a blueprint for regeneration

Tissue regeneration has been studied for hundreds of years, yet remains one of the less understood topics in developmental biology. The recent Keystone Symposium on Mechanisms of Whole Organ Regeneration, reviewed by Gregory Nachtrab and Kenneth Poss, brought together biologists, clinicians and bioengineers representing an impressive breadth of model systems and perspectives. See the Meeting Review on p. 2639

Evolutionary crossroads in developmental biology: annelids

Annelids (the segmented worms) have a long history in studies of animal developmental biology, particularly with regards to their cleavage patterns during early development and their neurobiology. As reviewed by David Ferrier, Annelida are playing an important role in deducing the developmental biology of the last common ancestor of the protostomes and deuterostomes.

See the Primer on p. 2643

Evolutionary crossroads in developmental biology: the spider Parasteatoda tepidariorum

Spiders belong to the chelicerates, which is an arthropod group that branches basally from myriapods, crustaceans and insects. Hilbrant, Damen and McGregor describe how the growing number of experimental tools and resources available to study Parasteatoda development have provided novel insights into the evolution of developmental regulation and have furthered our understanding of metazoan body plan evolution.

See the Primer on p. 2655

Also see the related Editorial by Nipam Patel, Development‘s evo-devo Editor.

(1 votes)

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The most striking realization I have had over the course of last four weeks spent at MBL, Woods Hole is how limitless is the scientific spirit . Pioneers of classical embryological manipulation techniques appreciating the importance of mathematical modeling, groups going to non-model organisms in search of an answer, groups identifying novel questions by merely observing or rather comparing differences between two organisms in one aspect of development, all are examples of the same. Working with a wide range of organisms we have been able to appreciate the diversity of body plan, and its molecular, cellular and behavioral attributes. It’s like learning is fun so, trying to create a five-limbed tetrapod and two-headed frog was fun but also every failed attempt made us realize the importance of temporal and spatial context in development. Not every experiment performed has to be hypothesis driven and so we see fish organiser grafted into frog and mouse organiser into chick, imagination and curiosity are the only drive here. We enjoy the freedom to explore and experiment. Faculties and TAs are available around the clock, eager to help better define the question and design experiments. This encourages to think and ask questions without bothering about practical limitations. A glimpse of the wonderful scientific outcome of this can be seen in the “Fish-bowl” previously known as “Sweat-box”, the one hour post-talk discussion session with the speaker. The speaker is bombarded with questions by students, not all of whom are working in the same field. Many of the questions, including the naive ones, provide novel directions or lead towards yet unexplored possibilities. It’s the most fulfilling one-hour of the day for me and I hope all my course-mates and faculties share the feeling.

Though I am part of a vertebrate developmental biology group, organiser grafts, tissue transplants, gastrulation, chimeras etc. have mostly been text book concepts for me. Learning these classical techniques and concepts from the experts in the field was overwhelming. As they went down memory lane, we learned the evolution of the field. Sitting through the talks we were introduced to the discovery aspects of many molecular and cellular phenomena that so far we have been reading as facts. How the field started from inquisitive observation and systematic documentation followed by attempts to interpret the same. Hypotheses were generated and tools to validate the hypothesis were created. Need based emergence and evolution of the fields of molecular biology, imaging, biomechanics, bioinformatics and so on took place. You are introduced to different model organisms, their advantages as well as limitations. Also to the most recent techniques available for different kind of expression and functional analysis for different organisms, along with feedback on the performance . You get to hear about the questions that led to adoption of non-model organisms in labs and that make groups run more than one lab spread across globe on seasonal basis. In the lab session, you find faculties and TAs happy to help you try any and every experiment you can think of, always ready with tips from their experience and demonstrations. This deroots almost any hesitation one has in working with new model organisms or trying different techniques. It’s all about daring to try something new and different combined with patience and perseverance. In the last two weeks I have had the privilege of working with five different vertebrate species with experiments ranging from classical grafting, skeletal preps., bead implantation to assess the morphogenetic potential of proteins and drugs, to laser ablation, mouse embryo culture, mouse in utero electroporation and TALEN injection in transgenic fish lines. Imagine !!!

You set up a time-lapse last night to capture cellular movements along with lineage tracing by injecting dye in a two-cell zebrafish embryo. Today morning you found that due to improper sealing , and subsequent evaporation of embedding media, you could not capture anything. You are very upset and sitting quiet and calm at the dining table. “What happened?”, comes from your friends. And then comes a long list of strange disasters, time-lapse of an unfertilized egg, time-lapse of a dead embryo, embryo crawling out of the field just few minutes into time-lapse and so on. You just can’t help laughing all your worries away and happily start the next attempt for the same experiment. The group has participants from places spread all over the world. Strangely, you don’t feel the diversity unless, one of your group members suddenly in the middle of the night in the confocal room, tired after a long day, starts speaking Pourtuguese. It’s only after looking at your expression-less face with wide open eyes that she recalls you being an Indian . You enjoy a refreshing laugh together and move on with your experiment trying to find the best possible orientation of the mouse embryo for the time lapse. That small element lying there somewhere deep within us which wants us to read “the mind of nature” is what connects us all beyond our differences.

(14 votes)

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Last week, I attended the “Growing a Human Part” talk at the Royal Institution, with talks by John Gurdon and Helen Blau. You can read the announcement on the Node, and find the summary below in my collected tweets.

The audience at the talks was quite diverse. There was a class of high school students, and many regular attendees of RI public events. Both speakers did a great job of explaining the basics of stem cell research and the state of the field of regenerative medicine.

At the end of the evening, John Gurdon had an ethical, philosophical question for the audience. Paraphrased, the question was as follows:

Suppose a six-month-old baby dies in an accident. Skin cells of the baby are saved and frozen. Assume that the parents can’t have any more children of their own, and that there are no technological barriers to human cloning. Would you be in support of the parents using the skin cells of their dead child to generate a “twin”?

You can read below (in the Storify) how the audience answered, but what do you think?

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Reflecting on all the great talks over the course of four days, this meeting has been one of the most enjoyable I’ve been to – I’m sure it was due to equal parts setting and participants. Having a small number of high caliber participants was amenable to lively follow-up discussions either over food, drink, or a friendly game of croquet – again kudos to the organizers and the Company of Biologists.  After yet another fantastic lunch we all abruptly disband to the four corners of the world, but, as someone once said, no party can last forever. Back to the lab, fresh with either new or more refined questions to test.

I leave you with some summary points that were articulated on the last day by Sir John Gurdon. Food for thought if you will.

What is the significance of epigenetic memory? To establish and stabilize the somatic cell identity?

However eventually all things will exchange because the marks that maintain this epigenetic memory are either dynamic or can be perturbed.

Hence, what determines the exchange or transition of epigenetic marks? And, what is the basis of resistance.

Until next time. Cheers.

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This year’s limb conference was held on the 3-7 June at the scenic Mont-Tremblant, Quebec in Canada hosted at Le Grand Lodge hotel. During the winter, it is one of North America’s most popular skiing destination, but during the summer periods, it becomes a stunning location with views across the mountains of trees and magnificent lakes (see photo).

The conference began with a welcome dinner followed by the evening keynote lecture chaired by one of the organisers, Jacques Drouin. Cliff Tabin unfortunately could not attend to give the keynote lecture, however Denis Duboule “stepped in” and gave a wonderful and exquisite talk on his group’s current work on chromatin remodelling and regulation of the Hox genes.

After a tasty continental breakfast with freshly made pancakes and waffles, the first session of the next day was on ‘Growth and patterning’ chaired by Laura Lettice. The standout talks from this session were by Rolf Zeller (looking at bovine limb development), Gregg Duester (role of retinoic acid in patterning), Sevan Hopyan (cell rearrangements in limb development) and Brian Harfe (role of SHH in early limb buds) with plenty of interesting questions following each talk. The second session on ‘Limb initiation and identity’ was chaired by Chi-Chung Hui, with great talks by Qiyan Mao (cell motility in the zebrafish limb bud) and Yasuhiko Kawakami (role of islet1 in mice hind limb development). The session was followed by the first poster session with attention-grabbing posters by Kelsy Lewis (3D atlas mapping musculoskeletal morphogenesis in mouse limb) and Mandy Mason (roles of 5’ Hoxd genes and Meis2 in bat wing) that drew in large audiences. The evening concluded with a 4-course meal with the main dish being salmon and peach sauce – who would have thought they go together. The free open bar was also handy, which meant unlimited beers and wine for everyone to enjoy.

The third day began with a session on ‘Patterning’ chaired by Benoit Robert with many distinguished speakers such as Marian Ros (5’ Hox genes regulating digits via Turing-type mechanism), James Sharpe (using computational model of digit patterning via Wolpertian positioning information with a Turing-type mechanism) – it is of a nice coincidence that we also celebrate 100 years of Alan Turing’s birth this year as well – and Elazar Zelzar (modulation of chondro-progenitor cells). After lunch, the session concluded with a roundtable discussion on ‘Thalidomide: 50 years later’ by Robert Seegmiller, Trent Stephens and Neil Vargesson. Also present at this discussion was Mercédes Benegbi, a Thalidomide survivor and from the Thalidomide Victims Association of Canada, who gave a very emotional talk on the background of the disaster that started 50 years ago. Very fittingly, she received the longest and loudest applause at the end and reminded everyone (should they have forgotten) why scientists do the research they do and prevent such events occurring again in the future. The next session was on ‘Genetics, human malformations and regeneration’ chaired by Sevan Hopyan with standout talks by Etienne Vincent (roles of BMPs and Msx1 on axolotl regeneration) and Alison Elliott (presenting two patients with longitudinal limb deficiency). The second poster session then followed with stimulating posters by Jessica Rosin (regulatory elements controlling expression of Shox genes) and Matthew Towers (temporal requirement of Shh in chick wing development) – the session was again accompanied with free alcohol.

The fourth day started with a session on ‘Epigenetics, the genome and development’ chaired by Marie Kmita with exciting talks by H. Scott Stadler (role of HOTCHON in chondrogenesis and patterning), John Cobb (characterisation of limb enhancer downstream of Shox2) and Miguel Torres (HoxA cluster epigenetic regulation underlies cell-autonomous generation of proximodistal patterning). Due to a free-slot in the timetable, it was suggested and agreed there would be a discussion by Miguel Torres and Gregg Duester on the role of retinoic acid in proximodistal patterning chaired by Jacques Drouin. Both speakers gave a short presentation outlining their cases on whether retinoic acid is required for proximodistal patterning which drew plenty of discussion from the audience. This was a ‘hot’ debate with many questions remaining to be answered; however it was fantastic to witness two leading scientists putting forward their data and their arguments. For me, personally, this was the talk that I will remember for a long time and was very privileged to have been of attendance. The last session was chaired by Gen Yamada on ‘Comparative approaches and evolution’ with talks by Marie-Andrée Akimenko (actinodins, a fish-specific gene family lost during fin-to-limb transition) and Nicola Illing (5’ Hoxd genes and Meis2 in the bat wing). After more than three days of fantastic talks, posters, food, debates and discussions, the evening ended with cocktails (or sparkling wine), announcement of prizes for talks and posters, the farewell dinner and a gathering around a bomb-fire on the beach. The next day, we all had to checkout of the hotel and depart to Montréal-Trudeau airport and return to our homes. Many thanks go to the organisers and sponsors for a wonderful conference and I hope to attend the next limb meeting in two years’ time, I believe, in Florida. My personal thanks go towards the travel awards I received to allow me to attend the meeting. This report will also be submitted to the BSCB newsletter.

(5 votes)

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Stem cells are often in the media and are promoted as wonder cells that can solve the problems of most diseases. The stories told throughout this film give the story of stem cells behind the hype and describes the  real state of stem cell research and therapies today as well as what we are aiming for in the future! My first thought after watching Stem Cell Revolutions was: wow, is education supposed to be this entertaining? Although I have been working in the stem cell field for a few years now, I learnt a lot from watching this film so a big personal thank you to the makers of the film- Amy Hardie and Clare Blackburn for producing a documentary that provides such amazing and enthralling insights into the stem cell research field.

Stem Cell Revolutions takes us on a journey that begins with how stem cells were discovered around 50 years ago following  the study of patients in Hiroshima who were suffering from radiation damage. Following research examining the “factory where blood cells are made” , the bone marrow, Canadian scientists Till and McCulloch discovered blood stem cells: the first discovery of stem cells!! The story moves on to the discovery of other adult stem cell populations and the development of therapies for example Howard Green’s work on skin grafts and then onto restoring vision in India using stem cells. This then brings us to possibly the most controversial stem cell category, embryonic stem cells, whose discovery is discussed by Sir Martin Evans, who won the Nobel Prize for medicine in 2007 for his discoveries involving embryonic stem cells.

We then change gears and move on to the fascinating story of  how Professor Shinya Yamanaka’s work in which adult cells e.g. skin cells can be turned into an embryonic stem cell-like state, which as Connie Eaves says “turned our understanding of human development on its head” . The field of iPSC research is a relatively new stem cell field and I think what is great in this section is that we learn that this work had its basis in the cloning work completed in frogs by Sir John Gurdon and the creation of Dolly the Sheep by Sir Ian Wilmut. The ending of the film is led by the interesting question ‘Where Could It Lead?’. I for one am excited by finding out where stem cell research leads us in the next decade. Furthermore, the challenges that the stem cell field faces in terms of restrictions by legislation, ethical issues and current limitations of stem cell technology are all dealt with in a manner that gives the truth behind sensationalism reported in the media.

The stem cell story is told via interviews with many of the key players who work at the cutting edge of stem cell research field from Connie Eaves to Sir Martin Evans and Austin Smith to Shinya Yamanaka, many of whom I have been lucky enough to learn from directly, and whose expertise and inside knowledge provide great strength to this film. Additionally, the documentary really shows of the global nature of stem cell research and how communications across the globe are leading to progression.  However, I believe the real genius in this documentary was the inclusion of acclaimed author Margaret Atwood, who provides a perspective from a non-scientist. I particularly enjoyed the challenging interactions between Margaret Atwood and Professor Austin Smith– director of the Cambridge Stem Cell Institute. Another great highlight is the animations and illustrations along the journey- stem cell biology really comes to life via these means. I have to admit I am not sure of the significance of the dancing man, or why we need to see Austin cycling to/from the institute, though the latter really did make me smile.

Stem Cell Revolutions gives us the current status of stem cell research in a captivating yet easy to digest manner and leads us into what is possible in the future! It is a must see for anyone who wants to learn about stem cell biology. It is amazing to think that many discoveries that lie in wait may be uncovered by a very simple question as posed by Margaret Atwood to describe the origins of both art and science:-“What if?”.

(6 votes)

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June marked the start of summer in the Northern Hemisphere, as well as the Node’s second birthday. We celebrated this occasion with… a plethora of conferences, courses, workshops, and job postings! It was our busiest month ever, in terms of site visits as well as in number of posts, so let’s see what everyone has been up to.

Courses
The annual Embryology Course started again this month in Woods Hole, and the first update from this year’s students comes from Andrew Mathewson.

“Time has become an abstract concept for my fellow students and me; it seems like we just got here and yet have known one another for months. We engage in science almost every hour of every day. There is no work – only play. I was imaging immunostained plankton on a new Nikon A1 confocal microscope at 3am Saturday morning. I would have gone all night except I did not want to miss Nipam Patel’s famous butterfly lecture at 9am the same morning. Again, this isn’t work. I want to be doing this – and so does everyone else here.”

Meanwhile, a record number of people voted for a Development cover from some of the images taken by last year’s students. This beautiful image of a ribbon worm pilidium larvae (left) won this round.

Registration is also open for another course at MBL: the Gene Regulatory Networks in Development course, starting in October.

Conferences and workshops
The International Society for Stem Cell Research holds its annual meeting. This year, the meeting was held in Yokohama, and even the Emperor and Empress of Japan were there! For a full recap, see the posts by James and Dongjin, and the collected tweets from the meeting.

Later that month, the Company of Biologists held a workshop on epigenetics in the south of England. The Company of Biologists workshops are invitation-only for speakers, but every workshop reserves a few slots for PhD students, postdocs and new PI’s, who can apply to attend. David, Roopsha and Emmanuelle were three of lucky attendees at this workshop, and they wrote about their experience on the Node. If you would like to attend a future workshop, please have a look at the upcoming workshops and find out how to apply.

At the start of June, the fourth annual Young Embryologist Meeting took place in London, and Sorrel reported on the day.

Research
Paul wrote about a new method to improve the quality of images taken with halogen light microscopes, and the effect this might have on developing nations:

“The pages of the Node itself are testament to the power of fluorescent imaging to inspire and delight. Wakayama’s team are hoping that inexpensive modification of existing halogen microscopes in schools and teaching labs will help bring science to life for the next generation of budding researchers.”

Also on the Node:
-Lots of new jobs on the jobs page

–Hope Beyond Hype – a graphic story about stem cells

-The role of TGFβ in zebrafish heart regeneration.

-Registration open for the International Chick Meeting and the Physics of Living Matter symposium.

(2 votes)

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