The European Court of Justice has today announced a landmark decision banning patenting of inventions based on embryonic stem cells. Several senior stem cell biologists have expressed their concern that the verdict, which is legally binding for all EU states, will drive development of stem cell therapies outside Europe.

You can read more about the case on eurostemcell.org here: http://www.eurostemcell.org/story/european-court-bans-stem-cell-patents. We’d love to hear your views – why not post a comment on our site?

And while you’re visiting eurostemcell.org, have a look around! We’ve been busy over recent months and we’ve got loads of new content: Interviews with scientists, fact sheets and new educational tools in our stem cell toolkit, to name but a few.

(2 votes)

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Teaching Tools in Plant Biology is an online educational resource published by The Plant Cell and the American Society of Plant Biologists.  Each Teaching Tool includes a set of about 100 PowerPoint slides, a review article suitable for undergraduates with hyperlinked reading lists, and a teaching guide that includes learning objectives and discussion questions. Each article is peer-reviewed and incorporates broad introductory materials as well as some in-depth analysis of key experiments, so can be tailored for use with a variety of students, and each is updated annually. Topics include Leaf Development, Epigenetics, Phytohormones, Why Study Plants and Genetic Improvements in Agriculture. Teaching Tools are available to personal or institutional subscribers of The Plant Cell, but the first six articles, including Leaf Development and Epigenetics, do not require a subscription. We also have a FaceBook page on which we highlight timely topics of interest to teachers of plant development, genetics, molecular and cell biology and physiology. Please have a look and use any materials you like. We’re always happy for feedback! Send comments to mwilliams@aspb.org.

(6 votes)

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What would you do if you were given $500,000 to fund your research for five years, with no strings attached –– no proposals to write, no progress reports to submit? If you were one of the recently announced recipients of the prestigious MacArthur fellowship you would be giving this question some serious thought.

Every year since 1981 the John D. and Catherine T. MacArthur Foundation recognizes exceptionally creative individuals by awarding them with $500,000 “genius grants”. According to the press release published on September 20th “MacArthur fellowships come without stipulations or reporting requirements and offer fellows unprecedented freedom and opportunity to reflect, create, and explore. All [fellows] were selected for their creativity, originality, and potential to make important contributions in the future.”

To be considered for the MacArthur fellowship requires a nomination.  However the identities of the nominators as well as the selection process are kept in complete secrecy.  Those who are selected for the award find out through an “out of the blue” phone call from the foundation two weeks prior to the official announcement. This year’s 22 recipients include a musician, a poet, a historian, an economist, a radio producer as well as 10 scientists.  Among them is Yukiko Yamashita a developmental biologist and assistant research professor at the University of Michigan who studies the mechanisms regulating stem cell division in the context of unperturbed tissue anatomy –– adult testes.

Getting the Call

When Yukiko received the phone call informing her about being selected and asking her asking her not to discuss it with anyone except her spouse until the official announcement, she had a hard time believing that it was not a scam. “I called my husband right after I hung up my phone call with the foundation and [he] seriously warned me that ‘if you get a second phone call asking your bank account and pin number, so that they can transfer the award money, don’t give it to them.’”

They did not ask for her bank info but did want to bring a production crew to her lab to film an interview for the foundation’s website.  “I had to ask the director of my institute if the production crew can come into the building to film me before the press release. We seriously have to worry about some activists against research blowing up the building. I didn’t want to be the stupid assistant professor who believed they are awarded a MacArthur ended up with destroying the entire institute.” When the names of this years MacArthur fellows were finally announced publicly Yukiko felt more relieved than ecstatic.

Yukiko completed her undergraduate and doctoral studies in Japan, at Kyoto University, followed by postdoctoral training with Margaret Fuller in the Department of Developmental Biology at Stanford University. In 2007 she established her own lab as an assistant research professor at the University of Michigan Medical School.

Choose Your Centrosome Wisely

Her current research, which has won her the recognition from the MacArthur foundation, combines cell and developmental biology and is focused on investigating molecular and cellular mechanisms governing stem cell behavior, using the Drosophila male germline stem cells (GSCs) as a model. Her lab is investigating how stem cell division is regulated and how different stem cell populations interact to maintain tissue stability.

During her time at Stanford, Yukiko made the discovery that the centrosomes of Drosophila male GSCs are non-randomly segregated during asymmetric division –– the older “mother” centrosome remains with the stem cell while the newly replicated “daughter” centrosome is inherited by the differentiating cell.

The GSCs in Drosophila reside in a niche composed somatic support cells called hub cells and cyst stem cells. GSCs attach to the support cells at their apical side and during cell division orient the mitotic spindle along the apical-basal axis.  The cells still attached to the hub after cell division maintain a stem fate, while the daughter cell, displaced from the hub, differentiates.

“Its been known for quite a long time in the cell biology field that mother and daughter centrosomes are a little different from each other. The newborn centriole in the centrosome takes more than one cell cycle to get fully mature,” says Yukiko. As the centriole matures it accumulates structures called subdistal appendages, which serve to anchor the microtubles forming the spindle. Mature centrosomes therefore have a stronger ability to anchor microtubules. “Because of this difference the mother centrosome always has higher microtubule nucleating capacity.” In fact Yukiko’s found that the mother centrosome is anchored by microtubules at the apical pole of the cell, near the hub. “That is why, we are guessing, the mother centrosome can stay close to the hub cells all the time.”

However this mechanism is not universal to all stem cells.  “In Drosophila neuroblasts, every single cell cycle the mother centrosome gets inactivated and the daughter centromosme gets activated and so, unconventionally, the daughter centrosome has higher [microtubule organizing center] MTOC activity. In the end the stem cell ends up inheriting the daughter centrosome all the time.” The reasoning for this switching is not known, however the trend is that the centrosome with higher MTOC activity is inherited by the stem cell.  “In one case, germ line stem cells maintain higher MTOC activity on the mother centrosome, but in the Drosophila neuroblasts they make daughter centrosome with high MTOC activity. Why this is happening we don’t know. But once you have high MTOC activity it looks like that’s going to the stem cell.”

How Do Chromosomes Fit Into the Picture?

Following Yukiko’s discovery about the non-random segregation of centrosomes other scientists in the field speculated that it might serve as a mechanism to selectively segregate chromosomes, perhaps keeping the original strands in the stem cell as proposed by the immortal strand hypothesis. Yukiko, however, was not convinced that this was the case and thought that a thorough analysis was required to prove or disprove the hypothesis –– something that she felt was lacking in some studies.

“We thought we really should address this question in our system, in which we can directly test this idea,” she says.  In early 2011 Yukiko’s group published a paper in the Journal of Cell Science reporting that the chromosomes of GSCs, unlike the centrosomes, are randomly segregated.  “I’m glad that we published this paper because I think [among] the immortal strand hypothesis papers, some are really good and the data appears really convincing, but some others are not really excluding alternative possibilities or different interpretations. I really wanted to propose some rigorous way of testing it. I’m not saying that the immortal strand [hypothesis] is not correct, but then to make it right, you have to examine every single possibility.”

Since that publication, a the graduate student pursuing this line of research in her lab has examined the segregation of each individual strand for all the chromosomes and  found that at this level of resolution only a small subset of chromosomes are selectively segregated, while the segregation of others is random.  “It looks like germline stem cells are segregating very specific strands with quite high bias only for some of  the chromosomes, but not others, so that at least suggests that cells have the machinery to distinguish one chromosome strand over the other and then segregate one into the stem cell in a biased way.”

This finding that the majority of the chromosomes are randomly segregated still leaves the question of why cells need to selectively segregate their centrosomes?  “Ultimately the question everybody is asking is: does the mother or daughter centrosome carry some information, not just microtubules?”

Yukiko doesn’t yet have the answer but can speculate about the possibilities.  “The centrosome itself [could be] associated with some sort of fate determinants. That is not unprecedented. Some fate determining mRNA is associated with just one centrosome during mollusk early embryogenesis.  [Another possibility is that] the centrosomes are used to distinguish two different sister chromatids, to segregate one strand over the other.  Why you have to distinguish one strand over the other strand of the chromosome? I don’t think its for the sake of an immortal strand, I don’t think its because of the DNA mutations or avoiding them, instead I think it’s some epigenetic information that they want to carry. It might be histone modifications or DNA methylation but we don’t have any evidence for that yet.”

Checks and Balances

In addition to their work on centrosome segregation Yukiko’s group is pursuing two other lines of research.  One is examining a novel cell cycle checkpoint, which ensures the correct orientation of centrosomes prior to cell division. “We published one paper suggesting the presence of a new checkpoint that, in GSCs, makes sure the centrosomes are correctly oriented before they get into mitosis. If the centrosomes are not oriented correctly, this checkpoint gets activated and then stalls the cell cycle before entering mitosis. We really want to identify the mechanism of how stem cells are sensing the correct orientation of the centrosome before getting into mitosis.”

The idea of a cell-cycle checkpoint is more at home with cell biologists and Yukiko thinks that it will take some time to convince developmental biologists that what they are describing is a real phenomenon. “I think its going to be a long way to really prove that this really exists, exactly how cells are sensing it, and what is the molecular mechanism, etc. It will probably take multiple papers and probably quite long time; at least five years if not 10 years.”

Yukiko also wants to understand how different stem cell populations interact in tissues and communicate to coordinate their replication and life cycles.  This is a new line of research for the lab and Yukiko wants to explore this direction in the coming years.

“[The Drosophila male gonadal] stem cell niche contains yet another type of stem cell called cyst stem cell. The germline stem cells and cyst stem cells have to coordinate their divisions somehow, we don’t know exactly how yet. Many tissues are made of cell types that are coming from different stem cell lineages. That means the decision of one single stem cell population cannot be enough to maintain the whole tissue. One stem cell population has to coordinate with another stem cell population to make sure that tissues are maintained as a whole. I’m very, very interested in how the stem cells are coordinating with each other.”

Follow Your Passion

What does getting the MacArthur fellowship mean for the future directions in the lab? Most importantly in means freedom to pursue any interesting outcomes that arise in research without the constraints of sticking to a proposed research plan.  “The whole idea of being a scientist is that you can’t really predict anything. If you’re working on something and the answer is so predictable, its quite boring.  Now I feel I do have the freedom to wander off a little bit from the original plan, because of course I didn’t propose anything for the MacArthur!”

Having a passion for science it vital for success as a scientist, but it doesn’t mean that your whole life has to be about work. Yukiko admits that she used to get worried when life’s distractions took too much time away from the bench.  What helped her to establish a career as an independent researcher and develop a life-work balance was learning “laid-back confidence” from her postdoc mentor Margaret Fuller.  “She’s a really good scientist but she is not obsessed by success. You can love science, but it doesn’t have to be your whole life. Other things enter your life that may take time away from the science, but don’t worry.  It might take you a little longer, but you will get to the point where you want to go if you just continue what you’re doing. That is something I learned from her.”

Yukiko spends her free time with her family and taking care of her six-year old daughter. I asked Yukiko if there is something people would be surprised to learn about her. “I am really obsessed with fossil hunting,” she said.  In Michigan, which used to be under tropical water millions of years ago, finding fossilized coral can be as easy as examining the pebbles on the road for a few minutes.  “It’s becoming a fun hobby for my daughter and me.”  After some thought she added: “And another thing my husband always teases me about ‘Where is this assistant professor who sleeps 8-9 hours a day?’ It’s how much I sleep every day!”

For more information:

Profile of Yukiko Yamashita on the MacArthur Foundation website

Press release from the MacArthur Foundation announcing this year’s fellows

Yukiko Yamashita’s lab webpage

References

Yadlapalli Swathi, ChengJun, YamashitaYukiko M. (2011). Drosophila male germline stem cells do not asymmetrically segregate chromosome strands. Journal of Cell Science, 124, 933-9.

Yamashita Yukiko M. (2010). A tale of mother and daughter. Molecular biology of the cell, 21, 7-8.

Yamashita Yukiko M. (2009). The centrosome and asymmetric cell division. Prion, 3, 84-8.

(4 votes)

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There are so many factors for a stem cell to consider when deciding cell fates.  A recent paper from Development discusses how the age of a stem cell can affect its future.

Neurons and glial cells are two major cell types in the nervous system, and both come from the many divisions of neural stem cells (NSCs).  The amazing plastic characteristics of NSCs drive a lot of excitement over their future use in regenerative medicine, but the complex gene network in vertebrates makes understanding NSC plasticity difficult.  Flici and colleagues recently published a paper on NSC cell fate decision-making in the simple CNS of fruit flies.  The transcription factor Gcm was already known to drive glial fate in NSCs.  Flici and colleagues found that overexpression of Gcm in NSCs forced a complete conversion to glial cells.  In addition, NSCs plasticity is affected by age—as NSCs get older, their ability to drive glial cell fates decreases.  After NCSs fell into a quiescent state at old age, Gcm overexpression was no longer able to force glial cell conversion, suggesting that temporal cues, not mitotic potential, drive NSC plasticity.  Finally, Flici and colleagues found that the Gcm-glial cell fate pathway leads to low levels of H3K9ac, which is similar to the low levels of histone acetylation seen in vertebrate glial cells.  In the images above, fly embryos are labeled to show neurons (green) and glial cells (purple).  Control embryos (left) have few glial cells, while embryos with Gcm overexpression (right) have many glial cells.  The longer the Gcm overexpression, the more glial cells develop at the expense of neurons (top is early, bottom is late).  Arrowheads show cells with markers for both glial cells and neurons, an intermediate stage in the conversion towards glial fate.

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

Flici, H., Erkosar, B., Komonyi, O., Karatas, O., Laneve, P., & Giangrande, A. (2011). Gcm/Glide-dependent conversion into glia depends on neural stem cell age, but not on division, triggering a chromatin signature that is conserved in vertebrate glia Development, 138 (19), 4167-4178 DOI: 10.1242/dev.070391

(2 votes)

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Here are the highlights from the current issue of Development:

New blood: vasculature restrains pancreas growth

Although the primary function of blood vessels is to provide organs with the oxygen and nutrients that are essential for tissue growth and maintenance, blood vessels also provide positive paracrine signals during early pancreas development. Now, Yuval Dor and colleagues report that, surprisingly, non-nutritional signals from blood vessels restrain pancreas growth later in development (see p. 4743). In gain-of-function experiments, they show that VEGF-induced hypervascularisation restrains pancreatic growth in embryonic mice. Conversely, the elimination of endothelial cells increases the size of embryonic pancreatic buds. Blood vessels, they report, restrict the formation of pancreatic tip cells, reduce pancreatic lateral branching and prevent differentiation of the pancreatic epithelium into endocrine and exocrine cells both in vivo and ex vivo. The researchers propose, therefore, that the vasculature controls pancreas morphogenesis and growth by reducing branching and by maintaining the undifferentiated state of primitive epithelial cells. These unexpected findings might have important implications for the derivation of insulin-producing β-cells from embryonic stem cells for the treatment of diabetes.

Hesr1 and Hesr3 regulate satellite cell fate

During postnatal growth, satellite cells (skeletal muscle stem cells) divide to provide new myonuclei for growing muscle fibres, but in adult muscle they are maintained in an undifferentiated quiescent state except during muscle regeneration. Notch signalling regulates stem cells in many tissues, including skeletal muscle, and here, So-ichiro Fukada and co-workers investigate whether the Notch target genes Hesr1 and Hesr3 are involved in the generation of satellite cells (p. 4609). They report that Hesr1 and Hesr3 are expressed simultaneously in neonatal and adult mouse satellite cells and show that, although Hesr1 and Hesr3 single-knockout mice have no obvious satellite cell or muscle regeneration abnormalities, the postnatal generation of undifferentiated quiescent satellite cells is impaired in Hesr1/3 double-knockout mice. Moreover, satellite cell numbers gradually decrease in Hesr1/3 double-knockout mice because of premature differentiation, and the mice develop an age-dependent muscle regeneration defect. Thus, the researchers conclude, Hesr1 and Hesr3 play crucial roles in skeletal muscle homeostasis by regulating the undifferentiated quiescent state of satellite cells.

Endothelial cell movements during angiogenesis

During angiogenesis, new blood vessels sprout from an existing vascular network, elongate and bifurcate to form a new branching network. The individual and collective movements of vascular endothelial cells (ECs) during angiogenic morphogenesis are poorly understood but, on p. 4763, Koichi Nishiyama and colleagues provide some new insights into these movements. Using time-lapse imaging and a computer-assisted analysis system to quantitatively characterise EC behaviours during sprouting angiogenesis, they show that ECs move backwards and forwards at different velocities and change their positions relative to each other, even at the tips of elongating branches in vitro. This ‘cell mixing’, which also occurs in vivo at the tips of developing mouse retinal vessels, is counter-regulated by EC-EC interplay via Dll4-Notch signalling and might be promoted via EC-mural cell interplay. Finally, the researchers show, the dynamic behaviour and migration of ECs contribute to effective branch elongation. Thus, cell behaviours during angiogenesis and other forms of branching morphogenesis might be more complex and variable than previously thought.

JAK/Stat signals touch Tinman’s heart

During Drosophila heart development, intercellular signalling pathways activate a conserved cardiac-specific gene regulatory network by inducing the expression of the transcription factor Tinman (Tin) in the dorsal mesoderm. Stat92E, the transcriptional effector of the JAK/Stat signalling pathway, is a direct target of Tin and, on p. 4627, Eric Olson and colleagues characterise JAK/Stat signalling during cardiogenesis for the first time. They show that Drosophila embryos with mutations in the JAK/Stat ligand upd or in Stat92E have non-functional hearts with luminal defects and inappropriate cell aggregations. The JAK/Stat pathway, they report, is active in the dorsal mesoderm when the initially broad mesodermal expression pattern of tin becomes restricted to cardiac and visceral muscle progenitors, which occurs after dorsal mesoderm progenitor specification. Finally, they show that JAK/Stat signals activate Enhancer of Split complex genes to restrict Tin expression, thereby regulating heart precursor diversification. Overall, these findings show that JAK/Stat signalling regulates heart development and identify an autoregulatory circuit by which tin restricts its own expression domain.

Careless tALK predisposes to neuroblastoma

Neuroblastoma, the most common extracranial solid tumour in childhood, arises from cells of the developing sympathoadrenergic lineage. Activating mutations in the gene encoding the tyrosine kinase receptor anaplastic lymphoma kinase (ALK) have been identified in both familial and sporadic cases of neuroblastoma so might Alk signalling control proliferation in this lineage? On p. 4699, Hermann Rohrer and colleagues report that forced expression of wild-type ALK or neuroblastoma-related constitutively active mutant ALK increases the proliferation of cultured immature chick sympathetic neurons and their expression of the proto-oncogene NMyc and of the neurotrophin receptor trkB. By contrast, Alk knockdown both in vitro and in vivo reduces sympathetic neuron proliferation. Furthermore, the Alk ligand Midkine (Mk) is expressed in immature sympathetic neurons, they report, and in vivo knockdown of Mk also reduces sympathetic neuron proliferation. Together, these results indicate that Mk/Alk signalling controls the extent and timing of sympathetic neurogenesis. Thus, the predisposition to neuroblastoma that is associated with activating ALK mutations might be the result of aberrant neurogenesis.

(Bell)ringing the changes in plant phyllotaxis

Complex networks of regulatory genes control morphogenesis but how are these networks translated into the local changes in tissue growth that shape multicellular organisms? Jérôme Pelloux and co-workers (p. 4733) have been investigating the modulation of phyllotaxis (the arrangement of leaves and flowers along plant stems) in Arabidopsis by the transcription factor BELLRINGER (BLR). In plants, the formation of new lateral organs depends on demethylesterification of homogalacturonan (HG), a major component of plant cell wall pectins. The researchers show that ectopic primordia form in the floral meristem of Arabidopsis blr mutants because of ectopic expression of the pectin methylesterase PME5, which changes the demethylesterification state of HG. Thus, BLR normally represses PME5 expression in the meristem, thereby influencing the establishment of the phyllotactic pattern. However, in the elongating stem, the researchers report, BLR activates PME5 expression to maintain phyllotaxis. These results identify BLR as an important component of the regulatory network that controls HG demethylesterification and, in turn, phyllotaxis in Arabidopsis.

Plus…

Coordinating cell behaviour during blood vessel formation

Geudens and Gerhardt review recent progress in our understanding of blood vessel formation, which has been driven by advanced imaging techniques and a combination of powerful in vitro, in vivo and in silico model systems.

See the Review article on p. 4569

An interview with Gordon Keller

Gordon Keller is Director of the McEwen Centre for Regenerative Medicine at the University Health Network in Toronto, Canada. His research applies concepts from developmental biology to the investigation of the lineage-specific differentiation of mouse and human embryonic stem (ES) cells. He became an Editor of Development in 2011, and recently we asked him a few questions to find out more about him and his research.

See the Spotlight article on p. 4567

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The final day of the meeting continued with vivid discussion and scientific exchange during the presentation sessions as well as during the breaks. Coming back to the initial focus of the meeting, today’s remaining topics centered on the fly as a model system to study fundamental regulators of cell proliferation.

Nic Tapon, at the London Research Institute, presented a synopsis of the Hippo signaling pathway and novel insights into its regulation. This inhibitory cascade of kinases is involved in proliferation control and is conserved in mammals including humans where it has been implicated in cancer and stem cell biology. In the absence of inhibitory Hippo signaling, Yorkie, a downstream co-activator of Tef/Tead transcription factors, translocates to the nucleus and promotes proliferation and can ultimately lead to tumor growth. However, the upstream regulation of the Hippo pathway is still unclear, although a number of links to epithelial polarity pathways have been demonstrated. Nic Tapon’s talk focused on unraveling the regulatory inputs upstream of Hippo using cell based RNAi screens. Subsequent discussion included references to the previous day’s discussion of apico-basal polarity proteins involved in murine retinoblastoma (Rod Bremner’s talk) and in growth control in the fly (Helena Richardson’s talk).

Related to this, and with similar immediate relevance for human cancer, Ginés Morata presented conceptual and experimental advance on the role of tissue-level signaling and proliferation control. Referring to a classic, yet continuously relevant, experiment conducted during his own graduate studies (Morata & Ripoll, 1975), he introduced the concept of cell competition as a means of growth inhibition. He showed in contrast to lethal giant larva (lgl) mutant clones, which are outcompeted and eliminated by apoptosis, lgl ras double mutant clones overgrow and form tumors with an efficiency which increases the more clones are induced. Even though lgl ras clones overgrow, cells at the clone edges of undergo apoptosis, which altogether suggests that there is a minimum number of highly proliferating mutant cells (a microenvironment) that need to be present in order to evade elimination by cell competition. In addition he presented data suggesting that the apoptotic cells themselves could promote the proliferation of neighboring cells by secreting growth-promoting factors.

Concluding the scientific program of the meeting, the academic organizers Anna Philpott (Cambridge) and Nancy Papalopulu (Manchester) summarized the main aspects and recurring themes of the meeting as well as the remaining challenges in the field.

While the meeting had been somewhat “neurocentric” the identified common concepts and mechanisms are applicable to other tissue and cellular contexts. Indeed, “neurocentricity” may be a result of the fact that these concepts and mechanisms have been best elucidated in the nervous system to date. One important notion was interaction between cell cycle regulators and components various signaling pathways. Moreover, an increasing emphasis is placed on understanding the temporal and spatial dynamics of cell cycle and differentiation mechanisms. Another interwoven thread was the significance of identifying similar or related mechanisms in a range of organisms, not only in the mouse, but in frog, fly and in mammalian stem cell systems.

The utility of meeting platforms such as this one were praised, referring to newly identified areas of joint interest between the attendants, and resulting in facilitation of collaborations and future research. Specific for this meeting format was the truly generous opportunity for interaction and scientific exchange. Practically equal time was allotted to the discussion as to the actual talk within the sessions. Moreover, extended coffee breaks and joint activities enabled the lively discourse of the participants coming from all around the world. It was acknowledged that the attending junior investigators and discussants brought a certain freshness and creativity to the table, beyond fostering their career development through immediate interactions and informal discussion with leaders in the field. In summary, the meeting very well matched the format of the company of biologists workshops. While it already fulfilled its aim of promoting the understanding of “growth, division and differentiation” during development, more benefit and spin-offs are likely to arise from the continued exchange between its attendants.

(1 votes)

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This is the first post of others to come on the first course on insect neuroscience and Drosophila neurogenetics in Uganda, that is being partially funded by The Company of Biologist. The motivation for organizing the course is that currently in East Africa, and most parts of Africa, research in experimental neuroscience is carried out mostly with rats, which are expensive. However, almost no one is using Drosophila, an inexpensive model organism that in Europe and the U.S is leading in neuroscience and basic medical research. The course will include theoretical and practical (laboratory) sessions. It is intended for graduate students and Junior Faculty who are interested or involved in teaching or doing research in neuroscience at universities in Africa. This year course will start next week, and thanks to the support from The Company of Biologist, we will be welcoming students from Uganda, Tanzania, Kenya, Malawi, Nigeria, and Cameroon. The people involved in the project include a local organizing committee that is taking care of all the organization in Ishaka (where the medical campus of the Kampala International University is based, place where the course will take place), and faculty: Dr. Baden,  Dr. Palacios, Dr. Martin-Bermudo, Dr. Vicente, and myself (Dr. Prieto Godino). I will post here some other general posts about the course, but if you are interested and you would like to know more about it, and how it is running everyday you can follow our Facebook or our blog pages.

(4 votes)

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As a follow up to Ben Martynoga’s post from yesterday, here is some more information on the topics covered in this excellent workshop that took place a couple of weeks ago.

After extensive revolutions around the cell cycle in many of the previous sessions, Ryoichiro Kageyama introduced quite a different rhythm to the meeting in the afternoon session where he talked about Hes1 oscillations in embryonic and adult neural stem cells. Ryoichiro showed impressive live-imaging data from reporter constructs that allow his lab to visualize these oscillations. Besides being an exciting thing to watch, these oscillations are also important to balance self-renewal and neurogenesis during development, as Ryoichiro showed.

The next talk of the session by Nick Monk then took quite a theoretical approach to the same topic. Instead of Western blots and fluorescent micrographs he showed a lot of colorful simulations, which he used to investigate how in theory the oscillators described by Ryoichiro can be built by connecting the different components of the Delta/Notch signaling system. Nick showed that communication between single cells can make a big difference to the oscillatory dynamics. Communication therefore is essential not only for scientists, but also for their study objects.
Marc Kirschner from Harvard Medical School then gave the plenary talk of the meeting. He presented a balance with which to weigh single cells, and described how it can be used to address a very fundamental question in cell cycle research: How are cellular growth and cell cycle integrated to control size variability in cell populations? His talk perfectly set the tone for the evening session, where the participants together aimed at identifying the future big questions in the field. What became clear is that we’ll probably move away from searching for more and more kinases and phosphorylation sites, but will rather focus on integrative approaches. We may for example aim at understanding how the modules that drive cell cycle and growth are integrated and exchange information, how cells generate, sense and react to tissue level signals, and how the characteristics of the cell cycle differ in development, tissue homeostasis and disease.

(2 votes)

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October 7 is Ada Lovelace Day, celebrating women in science and technology. This international day to promote gender equality in these fields was first held in 2009, and is named after Ada Lovelace. Ada Lovelace is considered to be the world’s first computer programmer – although in the 19th century, they weren’t called “computers” yet! Ada wrote algorithms for Charles Babbage’s “Analytical Engine“.

A few related resources to mark the day:
-The Journal of Cell Science‘s “Women in Cell Science” interview series by Fiona Watt.
-“Mothers in Science: 64 ways to have it all“, a free eBook published by the Royal Society and produced by Ottoline Leyser (who has a bit more to say on the topic in an upcoming interview with Development, so watch this space in a few weeks.)

Who inspired you?
In many areas of science, women are underrepresented at all levels. In other fields, such as chemistry or molecular biology, the distribution is still quite even among students, and then drops dramatically among more senior scientists. Developmental biology, on the other hand, seems to suffer less from a lack of women than many other areas of science. In 2010, more than half of the presidents of national developmental biology societies were women! In addition, quite a few women have made significant seminal contributions to developmental biology over the years and are role models to many: Nicole Le Douarin, Christiane Nüsslein-Volhard, or Anne McLaren (see also here), to name just a few of them – but there are many others!

The organisers of Ada Lovelace Day are asking people to “share your story about a woman — whether an engineer, a scientist, a technologist or mathematician — who has inspired you to become who you are today.”   So who is your female role model?

(2 votes)

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Better late than never! This excellent workshop took place a couple of weeks ago, but it is still nice to have a record of what was discussed, here on The Node.

Fabienne Pituello started the day by describing how the Shh pathway can induce cell cycle regulators such as Cdc25b to increase the rate of neurogenesis in the developing ventral spinal cord of the chick. In keeping with other talks throughout the meeting her data supports the idea that modulating the length of specific cell cycle phases can affect the outcome of progenitor division. Working in a completely different model, the Xenopus retina, Muriel Perron explained how Hedgehog signaling has a highly analogous function in promoting rapid, neurogenic divisions in her cellular system of choice. She went on to show that this pro-differentiation activity of Hedgehog is counteracted by Wnt signaling, which instead promotes stem/progenitor cell maintenance. Furthermore Wnt and Hh seem to mutually antagonize one another, probably via the induction of direct target genes that modulate the other pathway.

Bill Harris, who also studies the development of the retina, gave a very convincing illustration of just how powerful live imaging in vivo can be understand the real dynamics of cell cycle progression and cell fate choices. For example, a simple genetic reporter where PCNA is fused to GFP can be imaged to quantify how long individual retinal progenitors spend in each phase of the cell cycle in real time.

In keeping with the mainly retina-centric nature of this session Rod Bremner wrapped the session up by showing how the eye is also an excellent model system in which to study the susceptibility to and onset of tumours. Using the mouse as a model system he described his elegant genetic strategies to unravel how the members of the Retinoblastoma (Rb) family of proteins interact with various components of cell cycle and signaling pathways to carry out their vital functions as tumour suppressors.

(2 votes)

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