In the early ‘90s, the discovery of neural stem cells in the adult brain aroused hope to exploit these cells to treat neurodegenerative diseases or even induce brain regeneration. Yet, the real potential of these cells is still unclear. In the last 15 years we have learned that during development neural stem cells are an heterogeneous population of progenitors whose neurogenic potential is restricted by spatial and temporal patterning mechanisms. Many of these cells at the end of development stop producing neurons but begin to generate a closely related related cell type: the astrocytes. Interestingly, some of these astrocytes, derived from all the main domains of embryonic progenitors, continue to produce neurons throughout life, fueling not only our brain but also our regeneration dreams. Unfortunately however, the neurogenic potential of these neuronal progenitors is restricted to few neuronal types destined to the olfactory bulb and dentate gyrus, a drop in the sea of neuronal types that characterize the CNS. Yet, given that astrocytes are widely distributed in the adult brain, understanding if besides those located in the neurogenic niches other astrocytic populations may retain a neurogenic potential is a highly relevant issue. In the early studies on adult neurogenesis, all brain regions beyond the olfactory bulb and dentate gyrus were stigmatized as “non-neurogenic”. This concept derived from the observation that in mice and rats these regions do not show active neurogenesis and when transplanted with neural stem cells these cells differentiate only into glia.

More recently, comparative studies have shown that in other mammalian species, including humans, a low level of neurogenesis occurs also in “non-neurogenic regions” such as the striatum and to a lesser extent the neocortex. Most importantly, brain lesions un-hide such neurogenic activities also in laboratory rodents. In some cases the newborn neurons were proposed to be generated by local progenitors, and recently it has been shown that in the mice striatum after stroke these local progenitors are astrocytes (Magnusson et al., 2014). We also obtained similar results in an excitotoxic model of Huntington disease (Luzzati et al. under revision). The main problem of these findings is that the fate of the newborn neurons generated in “non-neurogenic regions” remains largely unknown, and the hypotheses regarding their possible function/s range from an attempt to brain repair to an aberrant phenomena. Indeed, in all models of neurogenesis in “non-neurogenic regions” newborn cells have a short life span and fail to express typical markers of the neuronal types that populate the regions in which they are generated.

In the last few years our lab contributed to these studies showing that in rabbits newborn neurons generated in the SVZ also migrate toward the frontal cortex (Luzzati et al., 2003; Luzzati et al., 2006), and that local progenitors in the striatum are able to generate neurons (Luzzati et al. 2006). We also demonstrated that both the SVZ and local progenitors produce neurons in the striatum of a model of striatal progressive degeneration in mice (Luzzati et al., 2011)

Lateral view of a 3D model obtained from coronal sections stained with the marker of immature neuroblasts DCX. The location of the reconstructed region is outlined in the upper model. Chains of DCX+ neuroblasts (red) are mostly restricted to the vPSB and in close contact with blood vessels (violet)

In this issue of Development (Luzzati et al. 2014) , we describe a new model of adult neurogenesis in the lateral striatum (LS) of the Guinea Pig that adds some important pieces to the puzzle. First, we show that the LS of the Guinea Pig contains neuronal progenitors, likely of astrocytic nature, that are quiescent at birth but become transiently activated around weaning. This observation challenges the classic idea that the mature brain parenchyma is not permissive for the activity of neuronal progenitors, and it is thus of great interest for stem cell research. At the same time, the more significant feature of a neuronal progenitor it is its cell fate potential. We thus followed the fate of new LS neurons with BrdU and lentiviral vectors and clearly established that these cells have a short life-span, and do not differentiate into striatal neurons nor express markers involved in their specification. Nonetheless, these cells acquire complex morphologies and we propose that they represent a novel cell type. Interestingly, new LS neuroblasts share several features with neuroblasts generated during striatal degeneration in mice, such as expression of Sp8, a tropism for white matter tracts, and a short life span. At least in the guinea pig, the transient nature of neuroblasts may be related to their transient production and strongly support a transient role in circuit remodeling. Future studies should clarify if these cells actually represent a new player for brain plasticity. Moreover, it would be also interesting to understand if this form of plasticity is present also in other mammals, including humans, and if it plays any role after lesion. A comparative framework will be essential to answer these questions.

Luzzati, F., Peretto, P., Aimar, P., Ponti, G., Fasolo, A., & Bonfanti, L. (2003). Glia-independent chains of neuroblasts through the subcortical parenchyma of the adult rabbit brain Proceedings of the National Academy of Sciences, 100 (22), 13036-13041 DOI: 10.1073/pnas.1735482100

Luzzati F, De Marchis S, Fasolo A, & Peretto P (2006). Neurogenesis in the caudate nucleus of the adult rabbit. The Journal of Neuroscience, 26 (2), 609-621 PMID: 16407559

Luzzati, F., De Marchis, S., Parlato, R., Gribaudo, S., Schütz, G., Fasolo, A., & Peretto, P. (2011). New Striatal Neurons in a Mouse Model of Progressive Striatal Degeneration Are Generated in both the Subventricular Zone and the Striatal Parenchyma PLoS ONE, 6 (9) DOI: 10.1371/journal.pone.0025088

Magnusson, J., Goritz, C., Tatarishvili, J., Dias, D., Smith, E., Lindvall, O., Kokaia, Z., & Frisen, J. (2014). A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse Science, 346 (6206), 237-241 DOI: 10.1126/science.346.6206.237

Luzzati, F., Nato, G., Oboti, L., Vigna, E., Rolando, C., Armentano, M., Bonfanti, L., Fasolo, A., & Peretto, P. (2014). Quiescent neuronal progenitors are activated in the juvenile guinea pig lateral striatum and give rise to transient neurons Development, 141 (21), 4065-4075 DOI: 10.1242/dev.107987

(6 votes)

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The Institut Pasteur (Paris, France) announces an international call for group leader positions in the field of quantitative biology and modeling in developmental systems. Successful applicants will be integrated into the cutting edge interdisciplinary environment offered by an internationally renowned institute combining fundamental and translational research, in an attractive location in central Paris, in close proximity to other major research centers. Candidates with both an experimental and theoretical background, using quantitative approaches and willing to develop multidisciplinary projects related to developmental processes are encouraged to apply.

Successful junior candidates [1] will be appointed with a permanent position, and as head of a group of 6 people. These groups will be created for a period of 5 years and may thereafter compete for a full research group.
Successful mid-career and senior candidates will be appointed with a permanent position, and as head of a research group of 8 to 12 people. The groups will be created for 10 years (mid-term evaluation at 5 years) with the possibility of renewal.
Candidates should send their formal applications by E-mail to the Director of Scientific Evaluation, Prof. Alain Israël, at the Institut Pasteur (qubimo@pasteur.fr).

Application deadline: February 6, 2015

Short-listed candidates will be contacted for interview.

Applicants should provide the following (in order) in a single pdf file:
1. A brief introductory letter of motivation, including the name of the proposed group. Candidates are encouraged to contact the head of the Search Committee Francois Schweisguth (fschweis@pasteur.fr) or the head of the Department of Developmental & Stem Cell Biology Shahragim Tajbakhsh for queries (shaht@pasteur.fr).
2. A Curriculum Vitae and a full publication list.
3. A description of past and present research activities (up to 6 pages with 1.5 spacing; Times 11 or Arial 10 font size).
4. The proposed research project (up 6 pages with 1.5 spacing; Times 11 or Arial 10 font size).
Junior candidates [1] should also provide:
5. The names of 3 scientists from whom letters of recommendation can be sought, together with the names of scientists with a potential conflict of interest from whom evaluations should not be requested.

[1] Institut Pasteur is an equal opportunity employer. Junior group leaders should be less than 8 years after PhD at the time of submission (Dec 31, 2014). Women are eligible up to 11 years after their PhD if they have one child and up to 14 years after their PhD if they have two or more children.

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We have previously posted about the workshop that Development organised in September, titled ‘From Stem Cells to Human Development’. We provided a general summary of the meeting, as well as an overview of the stem cells ethics discussion that took place at the workshop. In addition, we have just published a video on this workshop on our YouTube channel, in which we interviewed both the organisers and some of the attendees. This short video gives a flavour of the aims, content and atmosphere of the meeting, and we would like to share it with you here.

As it is mentioned in the video, we can now announce that, following the success of this workshop we will be organising a follow-up meeting in early 2016! Look out for more information about it soon. Development will also be publishing in 2015 a special issue on Human Development, so check our previous Node post for more information on this.
 

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Post-Doc position in models of pattern formation and morphogenesis

1.Job/ project description:

The main objective is to:

a) Develop mathematical models of organ development (starting with but no restricted to teeth, hair and wings).  The mathematical models include intracellular gene networks, cell signalling and extra-cellular signal diffusion, bio-mechanical interactions between large
collectives of cells (all in 3D) (see above publications for orientative examples)

b) Develop models about the evolution of gene networks and embryonic development.

Our aims and research is devoted to understand how animal structure and morphology arises during the process of develpment by interactions between genes, cells and tissues. This is certainly a very complex process that involves many different kinds of interactions happening in complex spatio-temporal settings. Mathematical models are a good way to integrate this complexity to try to understand the biological logic of how animals transform from simple oocytes to animals that are functional and architecturally complex.

Our models take as inputs known or estimated gene networks and the initial distribution of cells in space (in a given stage in development) and provide as a result the final organ morphology and patterns of gene expression in a given organ (in a given, latter, stage of development). Each model is simply a mathematical implementation of a hypothesis about how an organ develops. We construct these hypotheses, based on experimental work from collaborating groups, and implement them in a computational model. The advantage of computational models in respect to merely verbal arguments is that the models provide precise quantitative predictions that are more easily to unambigously compare with experimental results (from new experiments aimed at testing the hypothesis). Merely verbal arguments are more difficult to be proven wrong or right and get even difficult to express when the process under study involves a large number of cells in complex movement and communication between them (as it is often the case in development). These easily lead to largely unintuitive dynamics that are hard to analyze without quantitative models.

In addition, computational models allow to explore not only the wild-type but also, by variaton in the underlying gene network, the range of possible morphological variants (and how they change through development). The capacity to play with the parameters of the model allows us to actually understand its dynamics.

Ultimately, a model is simply a summary of what we think we understand about a system but that allows us to see if the underlying hypothesis could work. That the model works does not imply that the hypothesis is right, further experiments are required, but if the model can not produce the right wild-type it means that the underlying hypothesis is wrong or incomplete. In other words, what we thought we understood, we did not actually understand.

The biotechnology institute includes a range of experimental biologitst working on several systems. The supervisor will be Dr. Salazar-Ciudad but the PhD would include close collaboration with Jukka Jernvall group and would include collaboration with other developmental biologists in the center. In addition, Jernvall’s group includes bioinformaticians, morphometricians, paleontologists and other evolutionary and
systems biologists (in addition to developmental biologists). The work may also include, optionally, collaboration, and spending some time, in Barcelona.
The modeling can focus on gene network regulation, cell-cell communication, cell mechanical interactions and developmental
mechanisms in general and, optionally, artifical in silico evolution.

2. Requirements:

The applicant should be a biologists, or similar, preferably with a strong background in either evolutionary biology, developmental biology or
theoretical biology. Some knowledge of ecology, zoology, cell and molecular biology are also desirable.

Bioinformaticians, systems biologists or computer biologists that do not have a degree in biology or similar similar would not be considered
(this excludes computer scientists, physicists and engineers).

Programming skills or a willingness to acquire them is required.

The most important requirement is a strong interest and motivation on science, gene networks and evolution. A capacity for creative and
critical thinking is also desirable.

3. Description of the position:

The fellowship will be for a period of 2 years (100% research work: no teaching involved) extendable to 2 more years.

Salary according to Finnish post-doc salaries.

4. The application must include:

-Application letter including a statement of interests
-CV (summarizing degrees obtained, subjects included in degree and
grades, average grade)

-Application should be send to Isaac Salazar-Ciudad by email:

isaac.salazar@helsinki.fi

Foreign applicants are advised to attach an explanation of their University’s grading system. Please remember that all documents should
be in English (no official translation is required)

5. Examples of recent publications by Isaac Salazar-Ciudad group.

-Salazar-Ciudad I1, Marín-Riera M. Adaptive dynamics under
development-based genotype-phenotype maps.
Nature. 2013 May 16;497(7449):361-4.

-Salazar-Ciudad I, Jernvall J. A computational model of teeth and
the developmental origins of morphological variation. Nature. 2010
Mar 25;464(7288):583-6.

6. Interested candidates should check our group webpage:

http://www.biocenter.helsinki.fi/salazar/index.html

The deadline is 15 of August (although candidates may be selected before).

Isaac Salazar-Ciudad: isaac.salazar@helsinki.fi

(1 votes)

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Graduate position for a PhD in gene networks, pattern formation and morphogenesis

1.Job/ project description:

The main objectives of the PhD project is to:

a) Develop mathematical models of organ development (starting with but no restricted to teeth, hair and wings).  The mathematical models include intracellular gene networks, cell signalling and extra-cellular signal diffusion, bio-mechanical interactions between large
collectives of cells (all in 3D) (see above publications for orientative examples)

b) Develop models about the evolution of gene networks and embryonic development.

Our aims and research is devoted to understand how animal structure and morphology arises during the process of develpment by interactions between genes, cells and tissues. This is certainly a very complex process that involves many different kinds of interactions happening in complex spatio-temporal settings. Mathematical models are a good way to integrate this complexity to try to understand the biological logic of how animals transform from simple oocytes to animals that are functional and architecturally complex.

Our models take as inputs known or estimated gene networks and the initial distribution of cells in space (in a given stage in development) and provide as a result the final organ morphology and patterns of gene expression in a given organ (in a given, latter, stage of development). Each model is simply a mathematical implementation of a hypothesis about how an organ develops. We construct these hypotheses, based on experimental work from collaborating groups, and implement them in a computational model. The advantage of computational models in respect to merely verbal arguments is that the models provide precise quantitative predictions that are more easily to unambigously compare with experimental results (from new experiments aimed at testing the hypothesis). Merely verbal arguments are more difficult to be proven wrong or right and get even difficult to express when the process under study involves a large number of cells in complex movement and communication between them (as it is often the case in development). These easily lead to largely unintuitive dynamics that are hard to analyze without quantitative models.

In addition, computational models allow to explore not only the wild-type but also, by variaton in the underlying gene network, the range of possible morphological variants (and how they change through development). The capacity to play with the parameters of the model allows us to actually understand its dynamics.

Ultimately, a model is simply a summary of what we think we understand about a system but that allows us to see if the underlying hypothesis could work. That the model works does not imply that the hypothesis is right, further experiments are required, but if the model can not produce the right wild-type it means that the underlying hypothesis is wrong or incomplete. In other words, what we thought we understood, we did not actually understand.

The biotechnology institute includes a range of experimental biologitst working on several systems. The supervisor will be Dr. Salazar-Ciudad but the PhD would include close collaboration with Jukka Jernvall group and would include collaboration with other developmental biologists in the center. In addition, Jernvall’s group includes bioinformaticians, morphometricians, paleontologists and other evolutionary and
systems biologists (in addition to developmental biologists). The work may also include, optionally, collaboration, and spending some time, in Barcelona.
The modeling can focus on gene network regulation, cell-cell communication, cell mechanical interactions and developmental
mechanisms in general and, optionally, artifical in silico evolution.

2. Requirements:

The applicant should be a biologists, or similar, preferably with a strong background in either evolutionary biology, developmental biology or
theoretical biology. Some knowledge of ecology, zoology, cell and molecular biology are also desirable.

Bioinformaticians, systems biologists or computer biologists that do not have a degree in biology or similar similar would not be considered
(this excludes computer scientists, physicists and engineers).

Programming skills or a willingness to acquire them is required.

The most important requirement is a strong interest and motivation on science, gene networks and evolution. A capacity for creative and
critical thinking is also desirable.

3. Description of the position:

The fellowship will be for a period of up to 4 years (100% research work: no teaching involved).

The purpose of the fellowship is research training leading to the successful completion of a PhD degree.

Salary according to Finnish PhD student salaries.

4. The application must include:

-Application letter including a statement of interests
-CV (summarizing degrees obtained, subjects included in degree and
grades, average grade)

-Application should be send to Isaac Salazar-Ciudad by email:

isaac.salazar@helsinki.fi

Foreign applicants are advised to attach an explanation of their University’s grading system. Please remember that all documents should
be in English (no official translation is required)

5. Examples of recent publications by Isaac Salazar-Ciudad group.

-Salazar-Ciudad I1, Marín-Riera M. Adaptive dynamics under
development-based genotype-phenotype maps.
Nature. 2013 May 16;497(7449):361-4.

-Salazar-Ciudad I, Jernvall J. A computational model of teeth and
the developmental origins of morphological variation. Nature. 2010
Mar 25;464(7288):583-6.

6. Interested candidates should check our group webpage:

http://www.biocenter.helsinki.fi/salazar/index.html

The deadline is 15 of August (although candidates may be selected before).

Isaac Salazar-Ciudad: isaac.salazar@helsinki.fi

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4th – 7th February 2015

The major goal of this Fusion Conference is to bring together in a single forum the diverse group of researchers who study fibroblast growth factor (FGF) signaling. This will provide a unique opportunity to discuss new results and to target future research areas. Among the topics to be covered in this FGF signaling in adult tissue homeostasis, repair, regeneration and angiogenesis; 3)  aberrant FGF signaling in developmental/hereditary diseases meeting are: 1) the mechanisms by which FGF signaling governs organogenesis and tissue patterning during embryonic development; 2) the role of including skeletal syndromes, hearing loss and hypogonadism.

Target Audience

Reflecting the pleiotropic functions of FGF signaling in human biology, FGF researchers encompass a wide range of scientific disciplines, including structural biologists, biochemists, cell biologists, endocrinologists, developmental biologists, geneticists, pharmacologists and clinicians.

Important Deadlines

Early bird and Talk Submission deadline– 30 Nov 14

Poster Submission – 21 Nov 14

Last Chance – 28 Nov 14

Register at: https://www.fusion-conferences.com/registration28.php

(1 votes)

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Hello! We’ve got lots of new things to share, including a film and fact sheet combo that looks at cell fate, cell identity and reprogramming, a closer look at an unusual model organism, and an interview with stem cell scientist and Parkinson’s disease specialist Malin Parmar.

Also featured in this news update: schools outreach in Scotland and Spain, and six new Spanish translations.

As ever, we’re keen to hear from readers of The Node – on Twitter, Facebook, or via our website. You can get involved as a writer or translator, tell us about the stem cell events you’re involved in, make comments or suggestions, or just say hello! And for regular stem cell news, why not subscribe to our monthly newsletter?

Cell Fate: Journeys to Specialisation

EuroStemCell’s latest film looks at how specialized cells develop from stem cells.

Cell Fate: Journeys to Specialisation premiered in Heidelberg earlier this month, followed by a lively Q&A session with Andreas Trumpp, featured scientist Thomas Graf, and great questions from the audience.

Read more about the launch and the making of the film.

New fact sheet: Cell identity and reprogramming

Our body contains several hundred different types of specialised cells. Each cell has very specific features that enable it to do its job. Yet every cell in your body contains the same genes – the same biological ‘instruction book’. So what makes each type of cell different? And can we control or change cell identities? How might this help us develop new approaches to medicine? 

Read more

Snail fur: an alternative model organism for stem cell research

In this guest blog post Hakima Flici, a postdoctoral researcher at NUIG’s Regenerative Medicine Institute (REMEDI), tells us a bit more about her particular area of stem cell research…the model organism hydractinia echinata.

Read more

The work of this REMEDI lab also featured recently in a BBC Future news story, The animal that regrows its head (and in Spanish: El animal que regenera su propia cabeza)

Interview with Malin Parmar: cell therapy for Parkinson’s disease

Malin Parmar heads a research group focused on developmental and regenerative neurobiology at Lund University in Sweden. The ultimate goal of her research is to develop cell therapy for Parkinson’s disease.

At this year’s Hydra summer school we spoke to Malin about how she got started in stem cell research, what she’s working on at the moment, and her view of the prospects for treating Parkinson’s disease with stem cells.

Read more

Amazing stem cell questions at Inverkeithing High School

This Stem Cell Awareness Day PhD student Jamie Gillies joined Richard Axton and Cathy Southworth at Inverkeithing High School in Scotland to share with students the exciting world of stem cell biology and the work of being scientists. Here’s his account of the day, and the intriguing questions the students asked.

Read more

Transdifferentiation workshops for secondary students at CRG

The Centre for Genomic Regulation (CRG) in Barcelona has started the school year with a new workshop for high school students. The workshop is taking place every Thursday in the CRG Teaching and Training Lab facilities, a space specifically designed for the training of new researchers and for outreach activities.

Read more

Six new Spanish fact sheet translations

Muchas gracias to our translators!

• Reprogramación celular: como convertir cualquie célula del cuerpo en una célula madre pluripotente
• Investigación y terapia con células madre: tipos de células madre y sus aplicaciones actuales
• Ética y reprogramación celular: cuestiones éticas después del descubrimiento de las células iPS
• Nuevas herramientas para la investigación de enfermedades: células reprogramadas en modelaje de enfermedades
• Enfermedad hepática crónica: Como puede ayudar la medicina regenerativa?
• Infarto: Cómo pueden ayudar las células madre?

Subscribe and stay informed

EuroStemCell’s newsletter is sent out monthly – subscribe now for regular updates.

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Here are the highlights from the current issue of Development:

Meristem maintenance is KNOX so simple

Class I KNOX transcription factors, such as SHOOT MERISTEMLESS (STM) and KNAT1, are known to play a role in the plant shoot apical meristem (SAM), where they are thought to prevent differentiation and hence promote stem cell maintenance. Now, on p. 4311, Urs Fischer and colleagues uncover a role for STM and KNAT1 in another Arabidopsis meristem – the vascular cambium, which is a lateral meristem that gives rise to xylem and phloem cells. They first show that STM and KNAT1 are expressed in undifferentiated cambial cells but also in differentiated phloem and xylem cells. The researchers further demonstrate that xylem fibre formation is reduced in stm and knat1 mutants, suggesting that STM and KNAT1 promote the differentiation of cambial derivatives. In addition, they report that STM and KNAT1 regulate xylem differentiation via transcriptional repression of BLADE-ON-PETIOLE 1 (BOP1) and BOP2, which are not expressed in the SAM. Together, these findings demonstrate that, in contrast to their function in the SAM, STM and KNAT1 promote cell differentiation in the cambium, suggesting that the exact role of these transcription factors in other meristems needs re-examination.

TBX1: at the heart of epithelial properties

During its development, the heart tube undergoes rapid elongation, fuelled by the addition of cardiac progenitors from the second heart field (SHF). The gene regulatory networks governing SHF formation have been studied extensively, but little is known about the basic cellular features of SHF cells. Now, Robert Kelly and co-workers show that the transcription factor TBX1, which is implicated in both normal SHF development and congenital heart defects, regulates the epithelial properties of mouse SHF cells (p. 4320). Using immunofluorescence microscopy, they first show that SHF cells in the dorsal pericardial wall constitute an apicobasally polarised epithelium. Transmission and scanning electron microscopy reveal the presence of monocilia on the apical surface of SHF cells and of actin-rich filopodia on their basal surface. Using live-imaging of thick-slice cultures, the researchers demonstrate that these filopodia are dynamic, extending towards and making contact with surrounding tissues. Importantly, they report that TBX1 plays a crucial role in regulating these epithelial cell features; cell shape, cell polarity and filopodia dynamics are perturbed in Tbx1-/- mutants. These exciting findings suggest that TBX1-mediated control of epithelial state is crucial for heart development.

Mesogenin 1 masters the presomitic mesoderm

During development, neuromesodermal (NM) stem cells give rise to both neural cells and paraxial presomitic mesoderm (PSM) cells, but what dictates PSM fate? Here, Terry Yamaguchi and colleagues show that a single transcription factor – mesogenin 1 (Msgn1) – acts as a master regulator of PSM development (p. 4285). They show that the overexpression of Msgn1 in mouse ESCs cultured as embryoid bodies (EBs) is sufficient to drive PSM differentiation. Microarray and ChIP-seq analyses of Msgn1-overexpressing EBs confirm that Msgn1 controls the expression of key regulators of PSM development, including those involved in epithelial-mesenchymal transition and segmentation. Importantly, the researchers demonstrate that Msgn1 overexpression in NM stem cells in vivo biases fate towards the PSM; the contribution of these cells to the neural tube is reduced while the number of PSM cells is dramatically increased. Finally, the authors show that Msgn1 overexpression can partly rescue the PSM differentiation defects observed in Wnt3a−/− embryos, suggesting that Msgn1 functions downstream of Wnt3a as master regulator of PSM fate. Given the role of the PSM as a precursor for a multitude of cell types, this finding has important implications for the fields of cellular reprogramming and regenerative medicine.

Basonuclin 2: a regulator of spermatogenesis

Embryonic germ cells display strikingly different fates with regard to mitosis and meiosis, depending on their sex. In female mice, germ cells switch from mitosis to meiosis shortly after reaching the foetal gonad where they generate the lifelong pool of oocytes. However, in males, meiosis and mitosis are actively repressed, and germ cells remain quiescent in the gonad until birth, when they resume mitosis and start generating spermatocytes. Here (p. 4298), Philippe Djian and colleagues demonstrate that Basonuclin 2, an extremely conserved transcription factor specifically expressed in male germ cells, suppresses meiosis. More surprisingly, they also show that Basonuclin 2 is required for mitosis repression and, later in life, for meiosis progression during spermatogenesis and maintenance of the spermatogonial stem cells that ensure spermatocyte production during life. Furthermore, Basonuclin 2 is necessary for the expression of DNMT3L, a key protein that is involved in spermatogenesis, and for the repression of meiotic genes (Stra8, Msx1 and Msx2) that are normally expressed in female germ cells. These findings, which uncover a new regulator of male gametogenesis, are likely to further our understanding of spermatogenesis in humans.

From embryonic stem cells to gastruloids: early development in a dish

One of the first patterning events of embryogenesis occurs during gastrulation: three-dimensional (3D) cell movements reorganise the embryo, a mass of morphologically similar cells, into an axially organised structure with three germinal layers (endoderm, mesoderm and ectoderm). To date, two-dimensional (2D) culture models have failed to recapitulate such complex cell behaviours linking cell movement to cell fate. Here (p. 4231), Alfonso Martinez Arias and colleagues show that 3D aggregates of mouse embryonic stem cells cultured in mesendoderm-promoting medium undergo cell movements, axial organisation and germ layer specification, features reminiscent of gastrulation. They demonstrate that the expression of endoderm (Sox17, Fox2A) and early mesoderm (Brachyury) markers becomes polarised in these aggregates. Later, cells originating from the Brachyury-expressing ‘territory’ are extruded from the aggregate. These ‘gastruloids’ thus present a powerful tool that can be used to study early embryonic tissue specification in a dish, an unprecedented feat in vitro.

PLUS…

Reactive oxygen species and stem cells

Recent work suggests that reactive oxygen species (ROS) can influence stem cell homeostasis and lineage commitment. In this Primer, Ghaffari and colleagues provide an overview of ROS signalling and its impact on stem cells, reprogramming and ageing. See the Primer on p. 4206

Chemokines in development and disease:

In our latest poster and companion article, Wang and Knaut provide an overview of chemokine signalling and some the chemokine-dependent strategies used to guide migrating cells. See the poster on p. 4199

Leaf development and morphogenesis

The development of plant leaves follows a common basic program, which can be modulated to generate a diverse range of leaf forms. Bar and Ori review recent work examining how plant hormones, transcription factors and tissue mechanics influence leaf development. See the Review on p. 4219

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Chicken, quail, zebra finch, emu, duck, crow……a simple glimpse and we immediately realize how the Aves have, as a model system left their traces in various fields of biological research. And within the Aves class, the domestic fowl Gallus gallus is no doubt revered highly among the developmental biologists for their certainly distinguished career. Discovery of the germ layers, the src oncogene and B cells are only but a few examples (from a very extensive list indeed) of their notable contributions to scientific history.

How did chicks become so popular among members of our community? This preference appears to be rooted far back to antiquity, where even the ancient Egyptians showed an interest in “this bird that gives birth everyday”. Convenience in rearing and accessibility are decisive factors but for us developmental biologists, ease during embryo manipulation is a definite must. Our group released two methodological papers, both of which revisit the culturing and analyzing aspects of conventional embryo manipulation, all in hopes of making this tool more accessible to the avian community. So what`s new, then?

The paper, “Extending the limits of avian embryo culture with the modified Cornish pasty and whole-embryo transplantation methods” focuses on circumventing survivability restrictions of former ex ovo cultures with two technical alternatives, modified Cornish (MC) pasty culture and whole-embryo transplantation^1,2,3. To our knowledge, MC champions existing culture systems in convenience, cost and best ex ovo growth. What more could we ask for? Shaped in the form of a traditional British pasty, the embryo is folded along the medial axis with minute yolk portions packaged inside and cut along the edges to form a “sealed” vesicle. Intra-vesicular injection of yolk was an addition we found that resulted in faster growth and a greater percentage of embryos reaching HH18 with normal morphology. The growth potential of MC-cultured embryos can be further extended when combined with the in ovo whole-embryo transplantation technique. The neatness here lies in their compatibility with most common applications: targeted labeling, electroporation and imaging (facilitated by their exposed ectoderm surface) in early stages and phenotypic and functional analysis once cultured to later stages.

Figure 1. Parabiosed twins created by the MC method and cultured with whole-embryo transplantation.Left is quail, right is chicken.

Now, much can be done with a set of potent tools like these. Did we mention our attempts at making artificial twins? We practiced twinning by fusing two HH4 embryos first with the MC culture and later transplanting them back in ovo with the whole-embryo transplantation technique. Parabiosed twins are very rare in nature and highly valuable for hematopoietic studies (yes! there is a perfectly valid reason for making twins besides our personal pleasure).

By the way, have you ever heard of a chicken sexer? Although being one of those jobs hardly receiving limelight, it’s what gets eggs and chicken meat on household dining tables. Chicken sexers determine the sex of newly hatched baby chicks by sight alone. Male and female chickens have contrasting fates in the poultry industry; males become the majority of meat sold while females are passed on towards egg production. From a commercial and economical point of view, the faster the sexing the better. A commonly used technique originally developed in Japan in the 1930s is venting, where the cloacae of fluffy chicks are slightly opened to see inside their vent. Apparently, chicken sexers can distinguish 1,000 chicks on the hour with a 98% accuracy, which is simply incredible. So what does the remaining population lacking such ability do? Well, we hope to provide you with a solution below.

Figure 2. HINTW in situ hybridization labels female chicken embryos exclusively.

In our paper released earlier this year, “HINTW, a W-chromosome HINT gene in chick is expressed ubiquitously and is a robust female cell marker applicable in intraspecific chimera studies”, we introduce a promising alternative for the otherwise not so widely available ubiquitous-GFP chicken strains (due to country-wide quarantine regulations) for intra-specific chick/chick chimera studies ⁴. The essence of grafting and transplantation experiments depends on reliably distinguishing host and donor cell types. This HINTW (a W-chromosome gametolog of HINTZ) in situ hybridization probe detects female cells robustly and ubiquitously at early stages and most cells at later stages. When combined with male embryos pre-selected via a prior PCR screening step, it can be used to distinguish inter-sex donor and host tissues with outstanding precision, surpassing that of a chicken sexer.

Embryo manipulation is a toolbox full with the innovative ideas of our predecessor developmental biologists and we are very much delighted to be able to tip in. We would like to conclude by inviting anyone to our lab needing help with the manipulation techniques described in our published papers discussed above.

Maiko Sezaki and Hiroki Nagai

References:

1. Nagai, H., Sezaki, M., Nakamura, H., & Sheng, G. (2014). Extending the limits of avian embryo culture with the modified Cornish pasty and whole-embryo transplantation methods Methods, 66 (3), 441-446 DOI: 10.1016/j.ymeth.2013.05.005

2. Nagai, H., Lin, M., & Sheng, G. (2011). A modified cornish pasty method for ex ovo culture of the chick embryo genesis, 49 (1), 46-52 DOI: 10.1002/dvg.20690

3. Tanaka, J., Harada, H., Ito, K., Ogura, T., & Nakamura, H. (2010). Gene manipulation of chick embryos in vitro, early chick culture, and long survival in transplanted eggs Development, Growth & Differentiation, 52 (7), 629-634 DOI: 10.1111/j.1440-169X.2010.01198.x

4. Nagai, H., Sezaki, M., Bertocchini, F., Fukuda, K., & Sheng, G. (2014). HINTW, a W-chromosome HINT gene in chick, is expressed ubiquitously and is a robust female cell marker applicable in intraspecific chimera studies
Genesis, 52 (5), 424-430 DOI: 10.1002/dvg.22769

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As we’ve reported elsewhere on the Node (here and here), we recently held a very successful meeting ‘From Stem Cells to Human Development‘. As a direct result of the enthusiasm expressed at this meeting, we are now planning a Special Issue on the topic of Human Development, scheduled for publication in late 2015. Submissions must be received by January 30th 2015 for consideration for this Special Issue.

The issue will focus on the use of stem cell technologies to understand basic principles of human development. Until recently, our understanding of human embryogenesis has been hampered by the inaccessibility of the system, but recent advances in the stem cell field – most notably the generation of human pluripotent stem cells and the development of organoid culture systems – now allow us to investigate developing human tissues: providing insights into fate specification and tissue organisation, and informing our efforts to treat developmental disorders and develop regenerative therapies. Development sits at the heart of this field, with a strong interest in both developmental and stem cell biology, and covering both in vivo and in vitro systems.

For those interested, more details on this Special Issue can be found on our dedicated web page, or contact the Development office directly for any enquiries.

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