The massive cow femur I keep on a shelf right in front of me in my office clearly demonstrates that the shaft of a long bone is anything but a straight, smooth, symmetric tube. It is unevenly flattened and covered with ridges and grooves, bulges and depressions. This extremely intricate topography matches perfectly with adjacent organs and tissues, tendons and joints, thereby enabling the musculoskeletal system to perform its vital functions. Oddly enough, the mechanisms that sculpt the unique and elaborate surface of each bone have been largely overlooked by the study of bone development.

My lab has studied musculoskeletal development for quite a few years, focusing on aspects such as the contribution of muscle contraction to joint formation (Kahn et al., 2009) and the involvement of tendons and muscles in the development of bone protrusions (Blitz et al., 2009). Fascinated by the morphogenetic riddle of the circumferential shape of bones, I have assembled a multidisciplinary team of scientists and students to tackle it. I first approached Prof. Ron Shahar from the Hebrew University, a scientist, veterinarian and engineer, who is an expert in bone orthopedics and mechanobiology. Together, we brought in the then Ph.D. student Amnon Sharir, also a vet, who took upon himself to integrate the developmental and biomechanical aspects of the work. I also recruited specifically for this project Tomer Stern, then an M.Sc. student with a background in mathematics and informatics.

We began by developing scanning protocols and data processing algorithms for the analysis of bone development using micro-CT images. Soon enough, we discovered that the minute dimensions of embryonic mouse bones at the onset of ossification, the low and varying mineral levels and the complex and diverse morphology all presented major obstacles to our efforts. When we finally obtained the first lucid images of how a long bone is formed, our frustration turned into excitement. We could clearly see how a ring of mineral is formed around the developing cortex, followed by construction of perpendicular struts on which the next layer of mineral is laid. The bone shaft gradually became wider and the cortex thicker, until the latter was eroded from within to reach its final thickness.

A prominent and fascinating observation was that this process turned the circumference of the bone shaft from an almost perfect circle in the cartilage anlage, to the typical uneven outline of each fully ossified bone. Using a technique we had designed to visualize and quantify three-dimensional bone features by two-dimensional color maps, we realized that this shaping process involved nonuniform distribution of mineral deposition. We therefore termed this developmental program preferential periosteal growth.

Our next challenge was to uncover the regulatory mechanisms that underlie this morphogenetic process. Using muscular dysgenesis (mdg) mice, which lack muscle contractility, we showed that muscle-induced force is required for the mineralization patterns observed in wild type embryos and for the emergence of the resulting circumferential shape. Mechanical testing revealed that the properly shaped wild type bones had a larger load-bearing capacity. Finally, analysis of the distribution of osteoblasts showed that in bones that experience muscle loads, differential distribution of these bone-forming cells is responsible for preferential bone growth.

Our study expands the prevailing model of bone development by incorporating the contribution of periosteal bone formation, under regulation of muscle forces, to the shaping of the specific three-dimensional design of each long bone. Further study is required to uncover the entire molecular and cellular regulatory pathway that transduces mechanical signals into specific patterns of mineral deposition and bone formation.

Amnon Sharir, Tomer Stern, Chagai Rot, Ron Shahar, & Elazar Zelzer (2011). Muscle force regulates bone shaping for optimal load-bearing capacity during embryogenesis Development, 138 (15), 3247-3259 : 10.1242/dev.063768

Kahn, J., Shwartz, Y., Blitz, E., Krief, S., Sharir, A., Breitel, D., Rattenbach, R., Relaix, F., Maire, P., & Rountree, R. (2009). Muscle Contraction Is Necessary to Maintain Joint Progenitor Cell Fate Developmental Cell, 16 (5), 734-743 DOI: 10.1016/j.devcel.2009.04.013

Blitz E, Viukov S, Sharir A, Shwartz Y, Galloway JL, Pryce BA, Johnson RL, Tabin CJ, Schweitzer R, & Zelzer E (2009). Bone ridge patterning during musculoskeletal assembly is mediated through SCX regulation of Bmp4 at the tendon-skeleton junction. Developmental cell, 17 (6), 861-73 PMID: 20059955

(1 votes)

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

BMP signalling rolls up in the neural tube

During neurulation, polarised cell-shape changes at hinge points – specialised regions of the neural plate – help convert the neural plate into a tube. But how are these cell-shape changes regulated? To answer this question, Seema Agarwala and co-workers have been studying neural tube closure in the chick midbrain (see p. 3179). They identify a cell cycle-dependent bone morphogenetic protein (BMP) activity gradient in the anterior neural plate and show that it is required for ventral midline hinge point formation and neural tube closure. BMP signalling, they report, regulates the polarised cell behaviours associated with neural tube closure by modulating epithelial apicobasal polarity in tandem with the cell cycle. Because cell-cycle progression in the neural plate is asynchronous, BMP-mediated polarity modulation induces shape changes in only some neural plate cells, whereas their neighbours retain apicobasal polarity. This mosaic and dynamic modulation of polarity, the researchers propose, provides the neural plate with the flexibility to allow folding while retaining its epithelial integrity.

Tetraspanin-like protein regulates islet cell differentiation

The pancreas is a complex organ that contains ductal, exocrine and endocrine tissues. Here (p. 3213), Kristin Artinger, Lori Sussel and co-workers identify a role for Tm4sf4, a tetraspanin-like protein, during pancreatic endocrine differentiation. Tm4sf4 expression in mice is downregulated by the transcription factor Nkx2.2, which is known to be essential for islet cell differentiation. The researchers show that, in mice, Tm4sf4 is expressed in the pancreatic ductal epithelial compartment and is abundant in islet progenitor cells. Pancreatic tm4sf4 expression and its regulation by Nkx2.2 is conserved in zebrafish, and loss-of-function studies in zebrafish reveal that, in contrast to Nkx2.2, tm4sf4 inhibits α and β cell specification but promotes ε cell fate. Finally, in vitro experiments indicate that Tm4sf4 inhibits Rho-activated cell migration. The researchers propose that the primary role of Nkx2.2 during pancreatic development is to inhibit Tm4sf4 in endocrine progenitor cells, thereby allowing their delamination, migration and differentiation. Targeting Tm4sf4 could, therefore, provide a way to activate quiescent pancreas progenitors for the treatment of diabetes.

Feel the force: embryonic bone shaping

The vertebrate skeleton contains more than 200 bones, each with its own unique shape, size and function. Postnatally, bones remodel in response to the muscle forces they encounter. So bed rest, for example, causes bone thinning. Now, on p. 3247, Amnon Sharir, Elazar Zelzer and colleagues report that muscle force also regulates bone shaping during embryogenesis in mice. Using micro-computed tomography scans of embryonic long bones, the researchers identify a novel developmental programme that, through asymmetric mineral deposition and transient cortical thickening, regulates the specific circumferential shape of each bone. This programme of preferential bone growth, they report, ensures that each bone acquires an optimal load-bearing capacity. Moreover, the programme is regulated by intrauterine muscle contractions; in a mouse strain that lacks such contractions, the bones lose their stereotypical circumferential outline and are mechanically inferior. Thus, the researchers suggest, a reciprocal relationship between structure and mechanical load in utero determines the 3D morphology of developing bones.

Endoderm specification in sea urchins

In sea urchin embryos, endomesoderm specification involves β-catenin entry into the nuclei of the vegetal cells of the developing embryo. Now, on p. 3297, David McClay and colleagues reveal how the embryo uses maternal information to initiate this specification by showing that maternal Wnt6 is necessary for activation of endodermal genes. They report that the addition of Wnt6 or ectopic activation of the Wnt pathway rescues endoderm specification in eggs that lack the small region of the vegetal cortex that is normally needed for the activation of the endomesoderm gene regulatory network. This part of the vegetal cortex, they report, contains a high level of Dishevelled (Dsh), a transducer of the canonical Wnt pathway. They also report that morpholino knockdown of Wnt6 in the whole embryos of two sea urchin species prevents endoderm specification but not the expression of mesoderm markers. The researchers suggest, therefore, that maternal Wnt6 plus a localised vegetal cortex molecule, possibly Dsh, are necessary for endoderm specification in sea urchin embryos.

Gata-way to a cardiac progenitor fate

During gastrulation, cardiovascular progenitor cells (CPCs) migrate to the future heart-forming region of the embryo, where they produce the major cardiac lineages. But what regulates CPC fate and behaviour? On p. 3113, Ian Scott and colleagues report that Smarcd3b (Swi/Snf-related matrix-associated actin-dependent regulator of chromatin subfamily d member 3b) and the transcription factor Gata5 can induce a CPC-like state in zebrafish embryos. In mice, SMARCD3, GATA4 and TBX5 form a cardiac BAF (cBAF) chromatin remodelling complex that promotes myocardial differentiation in the embryonic mesoderm. The researchers now show that smarcd3b and gata5 overexpression in zebrafish embryos leads to the formation of an enlarged heart, whereas combined loss of smarcd3b, gata5 and tbx5 inhibits cardiac differentiation. Most notably, transplantation experiments show that cells overexpressing cBAF components migrate to the developing heart and differentiate into cardiac cells, even if initially placed in non-cardiogenic regions of the embryo. These results show that cBAF has a conserved role in cardiac differentiation and can promote a CPC-like state in vivo.

Aired out: FGF9 in lung development

During lung development, the secreted signalling molecule fibroblast growth factor 9 (FGF9) is expressed in both the mesothelium (the single layer of cells that envelopes the lungs) and the pulmonary epithelium (which gives rise to the proximal airways and terminal epithelial buds). Mesenchymal proliferation and epithelial branching are both reduced in Fgf9^–/– embryos, which die at birth because of impaired lung development. Intriguingly, David Ornitz and colleagues now show that mesothelial- and epithelial-derived FGF9 have distinct functions during lung development in mouse (see p. 3169). Mesothelial-derived FGF9 and mesenchymal WNT2A, they report, are required to maintain the mesenchymal FGF-WNT/β-catenin signalling pathway that is responsible for mesenchymal growth. By contrast, epithelial-derived FGF9 primarily affects epithelial branching, probably through regulation of BMP4 signalling. The researchers also show that epithelial and mesothelial FGF9 and mesenchymal β-catenin suppress the expression of the BMP4 antagonist Noggin in lung mesenchyme, thereby providing a mechanism for coupling mesenchymal and epithelial proliferation during lung development.

Plus…

In cycling tissues, stem cells coordinate tissue maintenance and repair. Here, Klein and Simons review the results of recent lineage-tracing studies and challenge the concept of the stem cell as an immortal, slow-cycling, asymmetrically dividing cell.
See the Hypothesis article on p. 3103.

The tenth annual Keystone Symposium on the Mechanism and Biology of Silencing convened in Monterey, California, in March 2011. Olivia Rissland and Eric Lai summarize the results presented at the meeting, which inspire and push this expanding field into new territories.
See the Meeting Review on p. 3093

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This is my personal report on the second of three laboratory projects which I have undertaken during the rotation year of my 4-year Wellcome Trust PhD. I studied how yeast come in more shapes and sizes than you might have imagined.

How do cells know which way is up? This is one of the most fundamental and important questions in biology. Almost every living cell has some degree of polarity, it has a front and a back or a top and a bottom, and they are very different from each other. In my second lab rotation I have been investigating how cells establish and maintain polarity, these distinct domains which do different things.

I have been working with a simple polarity model, the fission yeast Schizosaccharomyces pombe, which is not the same as the yeast you’d use to make bread. This yeast forms rod-shaped cells with growth zones at both ends that are very different from the sides of the cells, which don’t grow (Sawin and Tran, 2006). Yeast have cell walls, much like plants, and growth requires weakening of the cell wall and delivery of new components for cell expansion. This is dependent upon growth promoters, called polarity factors, such as the Tea complex in this yeast (Le Goff et al., 2006).

The delivery of polarity factors to the cell ends depends on the microtubule cytoskeleton, an array of protein polymers that exist in cells and provides transport routes for the controlled delivery of cell components to specific locations. My project has focused on the organisation of the microtubule cytoskeleton itself.

Microtubule polymers in S. pombe form bundles. Bundling is effected by two types of protein in the cell, one that actively slides fibres past each other (a ‘motor’ protein) and another that keeps microtubules attached to one another (Carazo-Salas, 2005). Previous experiments suggested that for the motor to organise microtubules in cells it concentrates at the outer ends of microtubules. However, how it gets there remained until now obscure. Using genetic techniques we were able to identify the protein that likely targets the motor protein to microtubule ends. Our finding is in agreement with work from a separate group of researchers who recently presented data at the 2011 British Yeast Group meeting.
Screening image

An example of an automatically captured image used to find strains with unusual cell shapes (grey regions) or microtubule organisation (white lines)

The lab has also begun systematically looking for genes which, when removed from the genome, affect the organization of the microtubule cytoskeleton or cellular shape and polarity. The regular rod shape of this yeast allows one to easily identify mutants that have altered morphology – in the past several well-known shape variants have been identified including bent, orb and T-shaped mutants (Hayles and Nurse, 2001). We have a collection of yeasts, each missing one gene from the genome, and have been systematically filming all of them using an automated microscope to see which ones have altered microtubules or cell polarity. This is something we’ve only just started and there is a lot of analysis to do with so many images – we are looking at over 3000 different strains – so there aren’t any exciting results yet. However, there are a lot of unanswered questions regarding cell polarity, and we are hopeful that our findings will help to address them.

What I have really enjoyed about working on this project is the involvement of computing in the work, because of how much data there is to analyse. I have been able to make useful contributions to the work the lab is doing, in the short time I have worked with them, by using my small amount of programming experience to develop several really useful software tools. When studying so many similar strains there are a lot of repetitive tasks to perform, which I have been able to automate, hence making everyone’s lives easier and improving productivity.

This post, and others about my PhD are also available on the Wellcome Trust blog here, here and here. I also hope to get back to doing some personal blogging now that the academic year is drawing to a close, so look out for new stuff here. For more about science in Cambridge checkout the science magazine, BlueSci.

References
# Carazo-Salas RE, Antony C, & Nurse P (2005). The kinesin Klp2 mediates polarization of interphase microtubules in fission yeast. Science (New York, N.Y.), 309 (5732), 297-300 PMID: 16002618
# Hayles J, & Nurse P (2001). A journey into space. Nature reviews. Molecular cell biology, 2 (9), 647-56 PMID: 11533722
# La Carbona S, Le Goff C, & Le Goff X (2006). Fission yeast cytoskeletons and cell polarity factors: connecting at the cortex. Biology of the cell / under the auspices of the European Cell Biology Organization, 98 (11), 619-31 PMID: 17042740
# Sawin, K.E., & Tran, P.T. (2006). Cytoplasmic microtubule organization in fission yeast Yeast, 23 (13), 1001-1014 DOI: 10.1002/yea.1404

(3 votes)

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I am the founder and CEO of DataGiving. I founded DataGiving whilst completing my Ph.D. in Genetics at the University of Cambridge. I have always been passionate about helping people. After completing my Bachelors degree in Psychology, I worked as an Assistant Psychologist at St Marys Hospital in London, helping adults with severe mental health disorders. Since I was a teenager I had aspired to become a Clinical Psychologist, but as much as I admired the great work Psychologists do, I didn’t feel that my desire to reach out and make a positive change would be fully achieved in this role. I returned to academia, as I had long been intrigued to learn more about the biological basis of human behaviour and cognition. I completed a Masters degree in Cognitive Neuroscience, at Imperial College London, which included a laboratory based research project at the Hammersmith Hospital, investigating the genetic basis of Parkinson’s Disease This research sparked my passion for genetics, and specifically the field of Epigenetics. I went on to be awarded an MRC scholarship, to undertake research into the imprinting regulation of Gsα in the laboratory of Dr Gavin Kelsey at The Babraham Institute, Cambridge.

Whilst at Cambridge, I was determined to fully participate in both academic and social life Cambridge University had to offer, and I served on my College graduate committee, was editor for the Graduate Union Bulletin, and was responsible for raising sponsorship for the Cambridge University Entrepreneurs Society (CUE). At Cue, I learnt about what was required to develop successful businesses, and met fellow students interested in entrepreneurship. I also worked for a while for a biotech, identifying collaborative opportunities with research labs around the world.

I have long been an advocate of harnessing creative and innovative technologies, to facilitate change for the common good. After a period of teaching myself basic computer programming, myself and a team of fellow Cambridge graduates won the TedxCam 2010 Open Data Challenge Hackathon, with a web data mashup named Ventropy (www.ventropy.org). Described by the BBC as “jaw-dropping”, Ventropy impactfully communicates the needs of grassroots businesses in mainly developing countries looking to raise funding through the microfinance site Kiva. Ventropy received high-praise from leaders from both the technology/web and charity fields, and is featured in the Kiva app portal. I was invited to speak about the inspiring idea at The Guardian Activate 2010 Summit, Technology, society and the future: Changing the world through the internet.

I went on to be awarded an UnLtd HEFCE Social Entrepreneurship Catalyst Award to develop the idea of Ventropy into a data visualisation app that translates the charitable impact of any amount of money, this can be seen at www.datagiving.com.

I am passionate about inspiring social entrepreneurs, and earlier in the year I was invited to speak to students at Cambridge University interested in ethical careers at the Beyond Profit flagship event, ‘From dream to reality – funding and support for social enterprise’, alongside UnLtd CEO Cliff Prior. I was also invited back to The Guardian Activate Summit in 2011 to take part in a stimulating panel debate discussing the power of data to save the world.

My scientific training has equipped me with an analytical mindset and curiosity that I’m able to apply in wider contexts of innovation. I am still very much passionate about biological science and in encouraging innovation in this field. I recently came runner up in an Open Innovation competition organised by MedImmune and Cambridge University Technology Enterprise Club, and I have since been asked by MedImmune to develop an Open Innovation strategy for MedImmune and the University of Cambridge.

My career to date has taken unexpected and unconventional twists and turns, but I’ve enjoyed every moment. Keeping an open mind and carving out your niche can be hard work, but incredibly rewarding.

(7 votes)

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There’s an interesting interview in Nature News, with Abdelali Haoudi – the vice-president for research of the Qatar foundation. Qatar opened a biomedical research institute a few years ago, and is now looking to expand this with a stem cell institute.

The situation in Qatar is almost opposite of that of many other countries:  they have enough money to set up the institute, but not necessarily enough highly-skilled people to work there. They’ve sent six students abroad to learn about stem cells at top institutes, and expect them to come back to work in Qatar, but will they really all come back, or is this going to be a practical lesson in the risks of “brain drain”?

The interview also addresses the ethical aspects and Islamic views of stem cell research. The foundation organised a conference for Islamic scholars to determine the fatwa (official Islamic rules) concerning human embryonic stem cells, and they came up with a set of well-defined rules: “We can use tissues from embryos for up to 14 days after fertilization. We have to get the consent of the parents. We cannot create embryos specifically for research, and we cannot use the tissues for commercial purposes — only for basic research or to develop new therapies”, explains Haoudi.

Have a look at the entire interview.

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The Embryology course at Woods Hole is still ongoing, and you can read more about what they’ve been up to so far in David Gold’s post.

The images below are the last of last year’s course images that have a chance at appearing on the cover of Development. Which of these images will be next to appear on the cover? Please vote in the poll below the images. (Click any image to see a larger version.) You can vote until July 26, 12:00 (noon) GMT

1. Drosophila larval body wall stained for tropomyosin (red), acetylated tubulin (green) and nuclei (blue, DAPI). This image was taken by Sylvia Bonilla (Purdue University) and Mazdak Lachidan (Samuel Lunenfeld Research Institute, Toronto).

2. Ciona embryo electroporated with Brachyury:RFP transgene. Nomarski image was used to create green overlay. This image was taken by Qinwen Liu (University of Maryland, College Park) and Xinwei Cao (St. Jude’s Children’s Research Hospital).

3. Mouse embryo. Wnt1/Cre-YFP transgene (yellow), 2H3 antibody (red), and DAPI (blue). This image was taken by Elsa Denker (Sars International Centre for Marine Molecular Biology, Bergen).

4. Live late stage squid embryo. This image was taken by Amber O’Connor (University of Alabama at Birmingham).

(3 votes)

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Twenty-four of us have been working for the past five weeks, studying development in a variety of contexts and organisms at the Marine Biology Laboratory in Woods Hole, Massachusetts.  The area is beautiful, but we don’t have much time to enjoy it.  This is a very intense course, we have lectures from 9am to noon, and then work on experiments often until 1 or 2 in the morning!  Because of this, we have been a little slow getting our blogposts going, but we look forward to sharing our experiences from Woods Hole.

Our course directors, Nipam Patel and Lee Niswander, presented the Embryology course as a chance to work with the latest techniques on model organisms (such as mice, and fruit flies), while providing a broad introduction to the diversity of animal evolution.  The first two weeks of the course exemplified these dual goals, as we studied some of the earliest branching animal lineages, and the two major invertebrate model systems.

At the beginning of the course Nicole King came to teach us how to work with choanoflagellates and sponges, while Uli Technau introduced us to the cnidarians (in particular the sea anemone Nematostella and the hydrozoan Hydractinia). Sponges and cnidarians are morphologically much simpler than most animals, and genetic evidence supports the long-standing hypothesis that they were some of the first groups to diverge from our own lineage.  However, sponges and cnidarians possess many of the genes  “higher” animals have, and they have provided important insight into the ways cells communicate during development.

Choanoflagellates are not actually animals, but DNA evidence suggests that they may be animals’  closest living relatives. Each choanoflagellate is a single cell. It has a long flagellum, which it uses to swim through the water and to trap bacteria (which it eats) in a collar made up of microvilli. The reason that choanoflagellates have received a lot of attention recently is that they don’t always spend life as a single cells.  Sometimes, as a choanoflagellate divides, the individuals stay connected to each other in long chains or rosettes.  Perhaps these organisms can teach us how the first multicellular animals evolved. Below is an image created by classmate Valerie Virta showing single and colonial choanoflagellates, the blue is staining the choanoflagellate bodies (DAPI), the red is microvillar collar (actin) , and the green is the flagellum (tubulin):

A team of scientists, including Joel Rothman, Dave Sherwood, and David Fitch, then came to teach us about the roundworm Caenorhabditis elegans. C. elegans has become a important model for understanding basic development.  Dave Sheerwood, for example, gave a great lecture on how the developing vulva of C. elegans may provide a better model for studying cancer than cultures of human tissues (you can find a podcast about his work here; look for the podcast from 5/10/10).

Finally, we got our hands on the invertebrate workhorse of genetics and developmental biology, the fruit fly Drosophila melanogaster.  It’s exiting to think that Thomas Hunt Morgan, the Nobel Prize winning founder of fruit fly genetics, did much of his research at the same institute we are working at now.  Nipam Patel, Lynn Cooley, Iswar Hariharan, and Matt Ronshaugen showed us a number of techniques for visualizing development, gene expression, and miRNA exoression in D. melanogaster, as well as how those techniques could be modified to look at other arthropods.  Below is a movie taken by David Gold of several Drosophila imaginal disks, stained with eyeless, cubitus interruptus, teashirt, and dapi:

We look forward to updating you with details about the third and fourth weeks soon.  More detailed posts will be available over time from David Gold’s blog at www.BioBlueprints.com.

(7 votes)

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Since its launch in June 2010, the Node has attracted thousands of visitors. Some have visited only once, others return every day. Some have written on the site, others only read. No matter which group you belong to, we now want to hear from YOU how your experience on the Node has been.

We’ve created a short survey, which should take no longer than 8 minutes to complete, to learn more about the Node’s readers, and find out how we can improve the site. The Node was launched in response to feedback from a community survey run by Development, so you can be sure that we take your feedback seriously in considering how to further develop the Node.

To thank you for your time and help, we’re holding a draw for a gift pack containing various items from the Node and Development – but you’ll need to complete the survey to be eligible!

Take the Node survey here.

We will be collecting responses until July 26th.

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As promised, in this final part of my meeting report on the BSCB-BSDB Spring Conference 2011 I will highlight a couple of talks which came with visual effects – studies involving live imaging. I prefer to watch these movies in seminars rather than downloading them with a paper because getting live explanations can make things clearer and more memorable for me. Drosophila was the main movie star, so this post will cover only fly studies.

Lucy Morris, a postdoc in Allan Spradling‘s lab (Carnegie Institution, Baltimore, USA), managed to develop a culture system that keeps the Drosophila germarium (the anterior tip of the ovariole) alive and developing for 14 hours. She used this to follow ovarian follicle generation in real-time: Every 12 hours, a new follicle is generated from a germline stem cell (GSC), which divides and migrates posteriorly, forming a cyst of 16 germline cells. While doing so, the cyst is wrapped by somatic escort cells, which midway through the germarium are replaced by a monolayer of somatic follicle cells. Escort cells have been proposed to arise from an escort stem cell niche at the anterior tip of the germarium and migrate along with the cyst, undergoing apoptosis after being shed. However, in her movies Lucy did not observe high levels of escort cell apoptosis, divisions or net migration! Rather, escort cells stayed still and let germline cysts pass them by using dynamic membrane protrusions to help them along. Lucy also found that escort cells do undergo rare divisions, but do so only to maintain a constant ratio of germ cells to escort cells.

After shedding the escort cells, the cyst is coated by a monolayer of follicle cells, which continue to encase the egg chamber until the egg is formed. This follicular epithelium carries integrins on its basal surface, which connect to the cytoskeleton and thereby mediate follicle cell migration over the extracellular matrix. Nick Brown (Gurdon Institute, Cambridge, UK) and his group imaged the movement and morphology of wild-type and mutant follicle cells to gain insight into the functions of specific integrin-associated proteins during this process. They identified a complex of proteins downstream of integrins that regulates actin stress fibres during a specific time point in development, leading to a sudden switch in the distribution of dynamic actin protrusions and a subsequent stop in migration – an observation that would have been impossible to make using fixed specimens only.

Arno Müller‘s (University of Dundee, UK) lab is interested in the mechanism of mesoderm layer formation and he presented movies in which they monitored the dynamic changes in morphology that the cells undergo during these tissue rearrangements. They found that the mesoderm cells change their migrational behaviour and morphologies during the process, with the consecutive phases having different requirements for the two FGF ligands, Pyramus and Thisbe.

Finally, germ-band extension was featured in more movies from the embryo, presented by Bénédicte Sanson (University of Cambridge, UK). During this process, the embryonic trunk elongates in the antero-posterior axis and narrows dorsal-ventrally. Bénédicte’s lab imaged the surface of wild-type and mutant embryos and automatically tracked cell movements and shapes to explain which cell behaviours lead to the net tissue deformation. These movies provided them with the data to conclude that both cell intercalation and cell shape changes contribute to the deformation in the fast phase of germ-band extension, whereas in the subsequent slower phase only cell intercalations are required. Polarised cell intercalation is directed by antero-posterior patterning, an intrinsic “force”. The changes in cell shape however can be explained by the invaginating mesoderm acting as an extrinsic force. Bénédicte therefore proposed that a balance between these two forces is essential for axis extension.

I learned from these and other talks that if you would like to know how cells behave in a tissue you will have to try to image them. Not only does this frequently result in spectacular movies, it also provides a lot of information in a very short time. Of course the imaging protocol first has to be established, a task that admittedly can present a whole PhD or postdoc project on its own – but more often than not, it seems to be worth the effort.

Morris LX, & Spradling AC (2011). Long-term live imaging provides new insight into stem cell regulation and germline-soma coordination in the Drosophila ovary. Development (Cambridge, England), 138 (11), 2207-15 PMID: 21558370

Clark IB, Muha V, Klingseisen A, Leptin M, & Müller HA (2011). Fibroblast growth factor signalling controls successive cell behaviours during mesoderm layer formation in Drosophila. Development (Cambridge, England), 138 (13), 2705-15 PMID: 21613323

Butler LC, Blanchard GB, Kabla AJ, Lawrence NJ, Welchman DP, Mahadevan L, Adams RJ, & Sanson B (2009). Cell shape changes indicate a role for extrinsic tensile forces in Drosophila germ-band extension. Nature cell biology, 11 (7), 859-64 PMID: 19503074

(2 votes)

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Last week I attended the 18th international C. elegans meeting at UCLA, organised by the Genetics Society of America. Having done most of my scientific training with mammalian cell culture, I had never been to an organism-specific meeting – let alone one about worms – and I was curious to find out what it would be like. I also wanted to learn more about the sense of community that exists among worm researchers, and what better way to experience that than by visiting their conference.

After the first day of talks, I had already spotted the community spirit in the presentation acknowledgements. The speaking slots were 12 minutes – 10 minutes to present, 2 for questions. That’s not exactly a lot of time to dwell on thanking everyone at the end, but they all did. In particular, almost everyone thanked the Caenorhabditis Genetics Center (CGC) for strains. However, in one of the opening talks of the meeting, Aric Daul of the CGC showed that people do tend to forgot to credit the centre in their publications. Since publication acknowledgements are a metric to ensure their continued funding, he urged people to not just thank the CGC in their talks, but also in their articles.

But nowhere was the community spirit of the worm people more obvious than in the social events. First of all, there were so many of them. I didn’t even manage to attend them all, but even after skipping two post-poster session socials, I still made it to the barbecue dinner, the Worm Art Show, the Worm Comedy Show, and the closing party. The party was unlike any conference party I had ever been to. Instead of the usual small wooden floor in a brightly lit dining hall, the worm party involved a huge ballroom, disco lights, and a packed dancefloor. Earlier that evening, the Worm Comedy Show, with Morris Maduro and Curtis Loer, had everyone laughing along at “The Lab” (a parody of the comedy “The Office”) and fake advertisements full of geeky humour (“UGG Tryptophane Boots”), and even singing along to “This Worm is My Worm”. The comedy show came just after the announcements of the Worm Art Show awards, but I’ll feature those in a separate post to highlight some of the art work.

There was science, too, of course. I attended most of the developmental biology sessions, but there were often two interesting talks at the same time. Still, thanks to modern technology you don’t have to miss a thing anymore: The meeting organisers encouraged people to use Twitter to share the meeting, and through there I could often see a glimpse of one of the parallel sessions. In fact, thanks to people eagerly tweeting bits of the meeting, I’ve managed to create a collaborative impression of the conference using Storify. See below to see the C. elegans conference through the eyes of Twitter users. (Make sure to click “load more” at the bottom. If nothing shows up below this paragraph, refresh the page. I’m new at using Storify so haven’t figured out if there’s a way to make it smaller on screen.)

(4 votes)

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