I expect many of you have already seen reports that the European Advocate General has taken a very restrictive view on patents for technologies that use human embyronic stem cells. This is the next installment in a long-running legal battle over a patent awarded to stem cell scientist Oliver Bruestle in 1999 and challenged by Greenpeace in 2004. Prof Bruestle and others are voicing serious concerns about the Advocate General’s postion (see news story at http://www.eurostemcell.org/story/european-advocate-general-critical-stem-cell-patents for example). Just wondered what Node readers think about all this?

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[updated 25/3/2011] Video was temporarily removed from Vimeo. Will repost it when it’s back up.

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The power of stem cells lies in the ability to give rise to many different cell types.  The stem cells found in the neural crest are no exception, and a recent Development paper describes the importance of Foxd3 in maintaining self-renewal and multipotency of these stem cells, and in regulating the fate choice of these cells.

After neural tube formation in the embryo, neural crest cells begin their migration away from the neural tube.  These cells generate a wide variety of differentiated cell types, including neurons, melanocytes, bone, smooth muscle, and cartilage.  Neural crest stem cells can be found in the neural crest population, yet the players regulating their self-renewal and multipotency were not yet understood.  Mundell and Labosky just reported the importance of a single protein – the forkhead transcription factor Foxd3 – in cell fate choice of the neural crest stem cells.  Without Foxd3, cells adopted more mesenchymal fates and cranial neural crest defects appeared.  In addition, Foxd3 mutant cultures of neural crest stem cells gave results showing that Foxd3 is important for maintaining the self-renewing and uncommitted multipotent state of the stem cells.  Image shows an 11.5 dpc cranial neural crest cell population with (left) or without (right) normal levels of Foxd3.  Without Foxd3, the increased appearance of Sox9 (red), marking osteochondral progenitors, suggests accelerated differentiation towards mesenchymal cell fates.

For a more general description of this image, see my post on EuroStemCell, the European stem cell portal.

BONUS!  The stunning unpublished image below, from the authors, shows a section through the headfolds in an 8-somite stage mouse embryo, with Foxd3 (red) and neural crest cells (green) labeled.

Mundell, N., & Labosky, P. (2011). Neural crest stem cell multipotency requires Foxd3 to maintain neural potential and repress mesenchymal fates Development, 138 (4), 641-652 DOI: 10.1242/dev.054718

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The 2011 Wellcome Image Awards were announced a few weeks ago, and developmental biology is well-represented in this year’s gallery, with images featuring cell division in plants, fish eye development, blastocysts, a developing mouse kidney, chromatin density in chromosomes, caterpillar prolegs, and a mouse embryo animation.

On February 23rd, the awards were announced at an official ceremony in London. “The awards ceremony was absolutely delightful”, according to Agnieszka Jedrusik, whose blastocyst image was amongst the winners, “Dr Laura Pastorelli should be congratulated on her amazing organizational skills. There were over 200 guests invited, yet, she still made an effort to greet all guests in person and made sure they felt welcomed.” Monica Folgueira, who is behind the winning cavefish image, also enjoyed the ceremony: “Everything went very quick for me. What I liked the most was having the opportunity of meeting the organizers and other creators.” Monica’s former lab mate Kara Cerveny was also amongst the winners, but she, unfortunately, couldn’t attend: “I’m now working at Cell as a scientific editor”, Kara writes, “and couldn’t make it back to London, but I heard that the ceremony was lots of fun.”

The Node spoke to Monica, Agnieszka and Kara to find out a bit more about them and their winning images. Click any of the thumbnail images to go to the high-resolution image in the Wellcome Image database.

Monica Folgueira
“I’m a lecturer at University of A Coruña (Spain). I just moved back to Spain last September after a postdoc at Steve Wilson’s lab (UCL). Now that I’m back in Spain, I will try to continue studying different aspects of the development and anatomy of neuronal circuits in the zebrafish brain, in collaboration with Steve’s lab. In addition, I’m interested in brain diversity and evolution. So I plan to perform studies of comparative neuroanatomy in a few species of fish, including cavefish.

My image is a confocal micrograph of a cavefish embryo at around five days post-fertilisation. The embryo has been stained with an antibody against a calcium-binding protein (in green) to show different neuronal types and their processes in the nervous system, and with an antibody against a component of tight junctions (zona occludens- 1, in red)

I produced this image during my postdoc at Steve’s lab (UCL). This image was produced after a set of experiments whose aim was to compare the morphology of the telencephalon between various teleost fishes (including zebrafish, cavefish and medaka).

I decided to submit this image because for me it brings together some kind of beauty and drama. I find it striking that, although it is an embryo, the combination of small eyes and strong jaws makes it look more like an adult fish. The image also reveals interesting characteristics of the anatomy in fishes, like the presence of taste buds outside the oral cavity.”

Agnieszka Jedrusik
“I gained my first degree (BSc in 2004 followed by MSc degree in 2006) in Developmental Biology from Warsaw University, in professor Marek Maleszewski group, investigating the nature of sperm activating factor during fertilization of the mouse oocyte. In 2006 I moved to Cambridge, to professor Magdalena Zernicka-Goetz’s group at the Wellcome Trust/Cancer Research UK Gurdon Institute, where I have just completed my PhD. Here, I am investigating the molecular and cellular mechanisms behind the first cell fate decision that generates pluripotent ICM and the differentiated extra-embryonic lineage, the trophectoderm.

My image shows a three-dimensional reconstruction of a mouse blastocyst. Blastocyst is an outcome of a pre-implantation development, a unique developmental phase characteristic for placental mammals such as mouse or human. In mouse, this phase encompasses a period of approximately 4.5 days and leads to formation of the first tissue types: outer epithelium, called the trophectoderm (TE; in white) and pluripotent group of inner cells, the inner cell mass (ICM; in red). Following implantation into the uterus wall, the ICM will form the fetus, differentiating into all tissue types of the body. TE, on the other hand, will give rise to extra-embryonic structures that support embryo development by mediating nutrients exchange between mother and the fetus and providing signals to pattern the embryo and segregate germ cell lineage. Understanding how these first tissue types emerge during early development becomes increasingly important in modern world, given growing interest in assisted reproductive technology (ART) and associated with it the need for optimizing culture conditions and assessing quality of the obtained embryos.

This image was produced by scanning the embryo with a confocal microscope to create multiple virtual sections, which were then reconstructed using 3D computer software.

I submitted it to the Wellcome Image Awards because I believe it is important that the general public realizes that the pre-implantation embryo is not just a group of pluripotent cells that will build the body of the future individual. In fact, approximately two-thirds of embryos’ cells at that stage are differentiated (the trophectoderm) and will build the extra-embryonic structures. It is important to realize that, given the fierce discussion on the moral aspects of the research on the embryo derived ESc.”

Kara Cerveny
“I’m a cell and developmental biologist with an interest in the developing nervous system. Up until a few months ago, I was a post-doc in Steve Wilson’s lab at the University College London where I studied the transition from proliferation to differentiation in the zebrafish retina.

This image highlights two separate populations within the zebrafish retinal stem cell zone, an area found in the region of the retina closest to the lens. The undifferentiated retinal stem cells are highlighted in red, while the cells that are beginning to differentiate are highlighted in purple. The central yellow region is the lens.

I took this image relatively early in my post-doc (nearly 5 years ago now) when I was working out the protocol of double in situ staining for fish eyes. This particular sample worked beautifully, and to be a bit creative and make a pretty picture to hang next to my computer, I cropped the original image so that only the top half was visible and then reflected it across the absissa to make the image you now see. Eventually, unmodified images similar to this one were used for a paper that was published in Development.

When I presented my work at the Fall 2010 BSDB sensory biology meeting last September, Laura Pastorelli, the image curator for the Wellcome Trust, asked me if I would be willing to submit this image to the Wellcome Image collection. I was surprised and very happy when I learned that my image had been chosen to be part of this year’s award series. I later learned that the judges had been captivated by the kaleidoscope effect created by the elongated retinal progenitor cells seeming to radiate from the lens (just like I had been several years before).”

(4 votes)

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The Third USNCB Symposium on Frontiers in Biomechanics: Mechanics of Development

June 21, 2011, Nemacolin Woodlands Resort, Farmington, PA

In the fields of tissue engineering, synthetic biology, and regenerative medicine, much can be learned by studying how nature creates tissues and organs in the embryo. Accordingly, the last decade has seen rapidly expanding interest among engineers in developmental mechanics. Sponsored by the United States National Committee on Biomechanics (USNCB), this Frontiers Meeting will bring together biologists, engineers, and biophysicists to discuss the state of the art and future directions in this exciting field. The meeting will have a single track of oral sessions and free communications presented in poster format.

For more information, please visit
http://www.engineering.pitt.edu/USNCB2011/

Conference Co-Chairs:
Larry Taber (lat@wustl.edu), Lance Davidson (lad43@pitt.edu)

(2 votes)

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Congratulations to Sarah A. Elliott (University of Utah) and Nobuo Ueda (University of Queensland), whose image of a sea urchin eating seaweed will appear on a cover of Development later this year.

Mouth of an adult sea urchin feeding on a fragment of seaweed.

The image is a still from this timelapse:

It was a very close race, with the image of the squid embryo, taken by Jennifer Hohagen (Georg-August-University of Goettingen), repeatedly in first place as well over the course of the voting period, but when the poll closed, the sea urchin was sixteen votes ahead.

The two other images in this round were of a Drosophila embryo, taken by James Tarver (University of Bristol), and a zebrafish embryo, taken by Ann Grosse (University of Michigan).

Altogether, more than four hundred votes were cast. The next round of voting will occur in a few weeks, when you’ll be able to choose between more beautiful images taken by students of the Woods Hole embryology course.

(3 votes)

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

A breath of fresh air: miRNAs regulate lung development

Throughout development, a proper balance between the proliferation and differentiation of progenitor cells is essential but the gene regulatory networks that control this balance are only partly understood. Here, Edward Morrisey and colleagues report that miR302/367 (a microRNA cluster) regulates the behaviour of endoderm progenitor cells during mouse lung development (see p. 1235). MicroRNAs (short RNA molecules that silence complementary target mRNA sequences) are expressed in clusters from a single primary transcript. The researchers show that, in early lung endoderm, the miR302/367 cluster is a target of the transcription factor Gata6, which is known to regulate lung endoderm progenitor differentiation and proliferation. Increased or decreased miR302/367 expression, they report, alters the balance of lung endoderm progenitor differentiation and proliferation in part through regulation of the tumour suppressor Rbl2 and the cell-cycle regulator Cdkn1a. Notably, altered miR302/367 expression also disrupts apical-basal polarity of endoderm progenitor cells. Thus, the researchers conclude, miR302/367 directs mouse lung development by regulating multiple aspects of lung endoderm progenitor cell behaviour.

Canonical Wnt9b signals size the kidney

During kidney development, the balance between nephron progenitor cell differentiation and proliferation determines the final number of nephrons and the ability of the kidney to function properly. One current model proposes that Wnt9b/β-catenin signalling induces differentiation in a subset of the progenitors, but that repression of this signal by the transcription factor Six2 is required for renewal of the remaining progenitors. On p. 1247, Thomas Carroll and colleagues challenge this model by showing that Wnt9b/β-catenin signalling is active in both differentiating and renewing progenitor cells in the developing mouse kidney. Moreover, rather than inhibiting Wnt9b signalling in the renewing cells, Six2 acts cooperatively with Wnt9b to elicit progenitor cell expansion. By contrast, in those progenitor cells where Six2 activity is low, Wnt9b/β-catenin signalling induces differentiation. Thus, the researchers propose, the response of progenitor cells to Wnt9b/β-catenin signalling depends on the cellular environment in which the signal is received, and canonical Wnt9b signalling is able to regulate both progenitor cell expansion and differentiation in the developing kidney.

Endoderm specifies germline niche

Interactions between tissue-specific stem cells and their local niche are vital for stem cell self-renewal and differentiation. But how are niches established? On p. 1259, Tishina Okegbe and Stephen DiNardo provide new insights into testis stem cell niche development in Drosophila. The stem cells in the fly testis, which sustain spermatogenesis throughout life, are clustered around a group of somatic cells (hub cells) that serves as a niche. The researchers confirm a previous report that Notch signalling is necessary for specification of mesoderm-derived somatic gonadal precursor cells to the hub cell fate but, unexpectedly, show that the endoderm adjacent to the developing testis supplies the Notch-activating ligand Delta. They also report that niche cell specification occurs earlier than anticipated, well before the expression of known niche cell markers. Given that mammalian primordial germ cells also pass through endoderm on their way to the genital ridge, the researchers suggest that Delta-Notch signalling by the endoderm could be a conserved mechanism for specification of the germline niche.

Glia shape up sensory neurons

Neuronal receptive endings (for example, sensory protrusions) are remodelled by experience; but how do they acquire their new shape? To address this question, Shai Shaham and co-workers have been studying the remodelling of sensory neuron receptive endings that occurs in C. elegans during dauer (a developmental state induced by environmental stressors). They now report that glial cells delimit this remodelling in response to external cues (see p. 1371). Nematodes have two AWC (olfactory) neurons, each of which is enveloped by an amphid sheath (AMsh) glial cell. The researchers show that AMsh glial remodelling is required for the shape changes in AWC sensory neuron receptive endings in dauers, and that glial remodelling requires the AFF-1 fusogen, the transcription factor TTX-1 and probably the VEGFR-related protein VER-1. The expression of ver-1, they report, requires binding of TTX-1 to ver-1 regulatory sequences, and is induced by dauer entry. Together, these results suggest that stimulus-induced changes in glial compartment size spatially constrain the growth of neuronal receptive endings.

Keeping an Eya1 on lung cell polarity

To function correctly, the epithelial cells that line the tubes and air sacs of mammalian lungs need to be polarised. Little is known about the mechanisms that control cell polarity in the lung epithelium but now, on p. 1395, David Warburton and co-workers implicate the protein phosphatase Eya1 in cell polarity control in the mouse distal embryonic lung epithelium, which represents the epithelial progenitor pool. The researchers show that distal embryonic lung epithelium is polarised with characteristic perpendicular cell divisions. They report that several spindle orientation-regulatory proteins and the cell fate determinant Numb are asymmetrically localised in distal embryonic lung epithelium. Furthermore, interfering with the function of these proteins in vitro randomises spindle orientation and alters cell fate. Importantly, the researchers show that interfering with Eya1 function in vivo or in vitro results in defective epithelial cell polarity and mitotic spindle orientation, disrupts Numb segregation, and inactivates Notch signalling, thereby establishing Eya1 as a crucial regulator of the complex behaviour of distal embryonic lung epithelium.

Heartfelt Slit/Robo signals

During vertebrate heart development, myocardial and endocardial precursors migrate towards the embryonic midline where they fuse into a linear heart tube. Now, Jason Fish, Stephanie Woo and colleagues report that a Slit/miR-218/Robo signalling pathway regulates heart tube assembly in zebrafish (see p. 1409). Members of the Slit family of secreted ligands interact with Roundabout (Robo) receptors to provide guidance cues during the development of several organs; development is also regulated by microRNAs (miRNAs) that can fine-tune the expression of developmentally important genes. The researchers show that the conserved miRNA miR-218 is intronically encoded in slit2 and slit3, and that it suppresses Robo1 and Robo2 expression. Further analyses indicate that Slit2, Robo1 and miR-218 are required for the formation of the zebrafish heart tube and that these factors act, in part, by modulating Vegf signalling. These findings reveal a novel signalling pathway for vertebrate heart tube formation and suggest a new paradigm of receptor/ligand regulation in which a ligand-encoded microRNA regulates the expression of its own receptor.

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Update 23/09/19: Please note that the below piece links to Dipity, a now defunct website. Over at the Drop In Blog you can read the story of what happened to the site. 

Science writer Ed Yong put together an interactive timeline of breakthroughs in the field of induced pluripotent stem cells (iPSC), inspired by a manifesto that called for more clarity in the media about the way scientific research is carried out. The timeline puts individual news articles about iPSC into a much broader context.

He only used key publications that were covered in the media, so not all studies are in there, but you can already see a story unfold if you browse along the timeline. Is there any study in particular that you think should be added?

(4 votes)

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The discovery of iPS made headlines the world over, and rightly so. But recently, transdifferentiation between somatic cell types has also been the focus of  considerable attention. A couple of Nature papers this year have reported that transdifferentiation is even possible between lineages arising from different germ layers – something that not everyone thought could be achieved (see Vierbuchen et al, Nature 463, 1035-1041 and Szabo et al, Nature 468, 521-526).

EuroStemCell aims to make this sort of cutting-edge scientific progress accessible to non-specialists, and to encourage discussion amongst the whole community. Thomas Graf has just written a short article on iPS versus transdifferentiation for eurostemcell.org. You can read the article at http://www.eurostemcell.org/commentary .

We’d love it if Node readers posted their opinions on the value and future of these two techniques as comments on the article. Just sign up to the site (a VERY simple, 2-minute process) and then go to Thomas Graf’s article and click ‘add a new comment’.

(1 votes)

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10 – 13 September 2011, Vienna, Austria

Featuring more than 120 world-class scientific speakers, including: Richard Axel, Susan Lindquist, Eric Wieschaus and Giacomo Rizzolatti.

Three plenary lecture sessions: microbiology of infection, genome evolution and neuroscience.

21 concurrent sessions juxtaposing classical fields of research with those exploring new frontiers in molecular biology.

Daily poster sessions, career skills development workshops and much more.

EARLY REGISTRATION: 15 MAY 2011
ABSTRACT SUBMISSION: 22 MAY 2011

To see the whole programme, to submit abstracts and to register visit: www.the-embo-meeting.org

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