Here are the highlights from the current issue of Development:

Neuronal cell fate: windows of opportunity

It is becoming increasingly evident that both vertebrate and invertebrate neural progenitor cells exhibit programmed temporal changes in their competence to generate specific neuronal cell types, but how is this competency controlled? Two articles in this issue address this question by studying Drosophila neuroblast lineage progression.

On p. 657, Michael Cleary and co-workers investigate the role of Polycomb repressor complexes (PRCs) in regulating neuroblast competence. In the Drosophila neuroblast 7-1 (NB7-1) lineage, the transcription factor Kruppel (Kr) specifies the third-born U3 motoneuron, but competence to generate U3 cells is limited to early divisions and is gradually lost when the neuroblasts transition to making interneurons. The researchers show that PRC loss of function extends the ability of Kr to induce U3 fate, whereas PRC gain of function causes precocious loss of competence to make motoneurons. The analysis of other neuroblast lineages that undergo a motoneuron-to-interneuron production transition demonstrates that PRCs also act to restrict motoneuron competence in these lineages. The researchers thus propose a model in which PRCs act to set up motoneuron-specific windows of competence in various neuroblasts that transition from motoneuron-to-interneuron production.

On p. 678, Stefan Thor and colleagues focus on the Drosophila embryonic neuroblast NB5-6T lineage to investigate how cell proliferation and cell fate specification are integrated during development. NB5-6T neuroblasts give rise to a lineage of 20 cells, including a differentiated set of neurons that are born at the very end of the lineage and that express Apterous: the Ap neurons. The authors identify two independent factors, Prospero and Notch, that act in concert to control the proliferation of NB5-6T daughter cells as the lineage progresses temporally; Prospero controls daughter cell proliferation in the early lineage and Notch activity then limits daughter cell proliferation in the late lineage, when Ap neurons are generated directly from neuroblasts, resulting in a programmed differentiation switch. Thus, the authors conclude, the control of neuronal daughter cell proliferation is integrated with temporal progression to ensure that the correct numbers of each unique cell type are generated.

Bypassing auxin signalling

Plant development is regulated by a number of mobile factors. The Arabidopsis BYPASS1 (BPS1) gene was previously shown to control shoot and root development by preventing formation of a mobile compound, but how this compound functions and whether it modulates other signalling pathways is unclear. Now, Leslie Sieburth and colleagues show that Arabidopsis BPS1, as well as two related genes, BPS2 and BPS3, control the production of a mobile factor, the bps signal, which regulates patterning and growth in parallel with auxin signalling (p. 805). By analysing single, double and triple mutants, the researchers show that all three BPS genes control bps signal synthesis. Importantly, bps triple mutants display severe embryogenesis defects, including disruptions to vascular, root and shoot stem cell populations. Finally, bps triple mutants exhibit normal auxin-induced gene expression and localisation of the PIN1 auxin transporter, suggesting that the bps signal functions in an auxin-independent manner. Although the nature of the bps signal remains unknown, these studies identify a novel pathway that regulates multiple stages of plant patterning and growth.

ABC of germline development

Plasma membrane ABC transporters serve dual functions in the cell: they export toxins to protect against damage and morphogens to mediate communication. It is thought that the activity of ABC transporters in embryos and stem cells should be high, so that mutagens are efficiently removed. Here, Joseph Campanale and Amro Hamdoun (p. 783) report the surprising finding that ABC transporter activity is reduced in germline precursors, the small micromeres, of the sea urchin embryo. This reduction in efflux pump activity can likely be ascribed to an increase in the rate of endocytosis specifically in the micromeres. What are the functional consequences of manipulating ABC transporter activity? The authors take a first step towards understanding this, showing that ABC transporter inhibition disrupts migration of the small micromeres at later stages of embryogenesis. While there is still much to be understood about the regulation and role of these plasma membrane pumps, this study provides evidence for the developmental importance of controlling their surface expression and activity.

Glutamate keeps hair follicles in touch

The hairs of our skin are mechanoreceptive: displacement of the hair is detected via sensory afferents in the hair follicle piloneural collar. In this complex structure, neurons, Schwann cells and keratinocytes are closely apposed, and interactions between these three cell types may influence differentiation and function of the piloneural collar. Here, David Owens and colleagues demonstrate that glutamate, which is known to mediate communication between neurons and Schwann cells in the central nervous system, has analogous activities in the periphery (p. 740). Signalling between VGLUT2-expressing neurons and NMDA receptor-expressing Schwann cells directs both formation and maintenance of the piloneural collar in mice. In conditional VGLUT2 mutants, the Schwann cells are disorganised and overall collar structure is severely disrupted. Moreover, treating the skin of adult mice with an NMDA receptor antagonist impairs touch-evoked responses, demonstrating defects in piloneural collar activity. Thus, continuous glutamate signalling between neurons and Schwann cells in the piloneural collar of the skin is essential for the integrity and function of this elaborate mechanosensory structure.

FGF signalling: keeping migrating cells on track

In Drosophila embryos, the longitudinal muscle cells surrounding the gut – the caudal visceral mesoderm (CVM) – arise in the posterior mesoderm and migrate anteriorly to reach their destination where they differentiate. Although this represents the longest cell migration event of Drosophila embryogenesis, the signals directing it are poorly understood. On p. 699, Angelike Stathopoulos and colleagues identify the FGF ligands Pyramus and Thisbe as crucial guidance cues for the CVM, signalling via the Heartless receptor to promote proper migration. The researchers use detailed live imaging and cell tracking analyses to describe wild-type migration, and analyse the consequences of disrupting FGF signalling, revealing defects in migration speed, directionality and cell survival. Intriguingly, by manipulating both the levels and location of ligand expression, they provide evidence for synergistic effects of Pyramus and Thisbe, although the mechanistic basis of such synergism remains to be investigated. Together, these data establish a new system for studying collective cell migration, and suggest additional complexities in FGF ligand-receptor interactions and signalling.

Plus…

Patterning embryos with oscillations: structure, function and dynamics of the vertebrate segmentation clock

The segmentation clock is an oscillating genetic network thought to govern the rhythmic and sequential subdivision of the elongating body axis of the vertebrate embryo into somites. Recent work, reviewed here by Oates et al, has provided evidence for how the period of the segmentation clock is regulated and how this affects the anatomy of the embryo. See the Review article on p. 625

Myoblast fusion: lessons from flies and mice

The fusion of myoblasts into multinucleate syncytia plays a fundamental role in muscle development and function. Here, Abmayr and Pavlath review the molecular events that drive myoblast fusion in the Drosophila embryo, in developing and regenerating mouse muscle, and in cultured muscle cells. See the Review article on p. 641

(1 votes)

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Postdoctoral Position in Chordate Comparative Embryology

A recent PhD or junior-level Postdoctoral Fellow is sought to join the Rui Diogo laboratory, at the Howard University College of Medicine, Department of Anatomy (Washington DC).

We are interested in a candidate that will contribute to uncover evolutionary and developmental mechanisms underlying both hard tissue (cartilages and bones) and soft tissue (mainly muscles) formation and patterning during ontogeny of a wide range of vertebrate taxa, as well as soft tissue in non-vertebrate taxa such as sea squirts. Some of the issues and broader questions in which we are particularly interested include: the parallelism between ontogeny and phylogeny, the remarkable similarity between the hard and particularly the soft tissues of the upper and lower limbs of tetrapods, the importance of evolutionary reversions/neotenic events, the study of birth defects and their implications for medicine and for the understanding of evolutionary biology, and the regeneration of hard and soft tissues in key vertebrate taxa. For more information about these subjects and about other issues being studied in the lab, please see www.ruidiogolab.com.

The successful candidate will have a PhD degree with a broad experience in molecular biology and developmental biology (e.g., doing/using developmental techniques such as antibody staining, in situs, and cell tracing, among others), backed by publications in peer-reviewed 
journals, and also some experience in comparative anatomy. He/She will have the skills and motivation to pursue a career in research, be interested in studying and comparing a wide range of taxa and various model organisms and in discussing various evolutionary and developmental issues.

There are funds available for two years, the first contract being for one year, the second contract depending on the productivity, interest and dedication of the candidate. There are possibilities to continue being part of the lab after the two-year period of the post-doc position. The post-doc will also have the opportunity to take classes, and then to be instructor, of human gross anatomy; this will further allow him/her to also postulate for faculty positions in medical schools in the DC area (including Howard University) as well as in other regions.

Interested candidates should send a CV including research interests, a list of publications and the names and contact information for three references to Rui Diogo, at rui.diogo@howard.edu. Please write “post-doc in Diogo’s lab” followed by your last name in the email subject.

Howard University is a historical University situated in the center of Washington DC, which is a beautiful, green and enjoyable city with numerous cultural and outdoor activities. The Department of Anatomy provides a prosperous, resourceful and multidisciplinary environment for biomedical research, includes faculty with a broad experience in developmental biology, paleontology, neurobiology, comparative anatomy and medicine. We have strong ties with surrounding institutions, particularly with George Washington University, and the candidate will probably have the opportunity to do part of his/her research at those institutions and thus to expand his/her knowledge and academic connections.

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If you’re interested in the role of the internet in science and science communication, you should keep an eye on Twitter from today until Saturday. Specifically, the tag #scio12, which is being used by the annual Science Online conference in North Carolina.  (Here’s the link to see the newest tweets tagged #scio12, but I’ve also collected a few interesting ones in the Storify shown at the end of this post.)

I’m not attending this year, but I’ve been a few times before. The meeting is very broad, covering scientific publishing, data sharing, blogging, science journalism, science art and everything in between. The thing that sets it apart most from many scientific conferences is that many of the participants know each other very well, personally, but have never met. The meeting originated as “science blogging” conference, and brought together people who had been talking to each other online for months or years. As a result, in between serious discussions titled “Self-censorship in physician writers” or “Using altmetrics to track the online impact of your research” the schedule leaves room for social events, and participants have been planning podcasts and chocolate swaps for months. For many people, this conference is the event of the year, where they get to see old friends again. For others, it’s a place to promote their latest science book, to introduce their new software for scientists, to recruit science communicators, or simply to take a step back from their research and look at science from a new angle.

The several hundred tickets for the conference sold out within minutes, so there’s a good chance that, like me, you’re not there. I’ll do my best to follow the meeting over Twitter the next few days, and collect the most interesting things in the Storify below. Join me in following along with Science Online online!

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(2 votes)

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BASIC SCIENTIST

ASSISTANT, ASSOCIATE, or PROFESSOR

DEPARTMENT OF OTOLARYNGOLOGY / HEAD AND NECK SURGERY

STANFORD UNIVERSITY SCHOOL OF MEDICINE

Faculty Position in the University Tenure Line- Basic Sciences

Stanford SOM

The Department of OHNS (http://med.stanford.edu/ohns/) is recruiting for a basic science tenure-track faculty position.  The successful candidate will be appointed at the level of assistant, associate, or full professor.

Scientists from a wide variety of disciplines are welcome to apply as long as their research relates to issues relevant to otolaryngology.  A few illustrative fields include developmental biology, genetics, molecular and cellular biology, biophysics, cancer, auditory physiology, voice physiology, auditory and vestibular prosthesis development, bioengineering, stem cell and gene therapy.  Collaborations with academic clinicians is encouraged.  The successful researcher will be part of an interdisciplinary and collaborative team in a lab close to Stanford campus with ample opportunity for interaction with a broad spectrum of scientists including world-class programs in neuroscience, genetics, biomedical engineering, and bioinformatics, to name a few.

Resources available include substantial funds for equipment acquisition and program initiation, as well as appropriate laboratory facilities.

The predominant criterion for appointment in the University Tenure Line is a major commitment to research and teaching.

Stanford University is an equal opportunity employer and is committed to increasing the diversity of its faculty.  It welcomes nominations of and applications from women and members of minority groups, as well as others who would bring additional dimensions to the university’s research, teaching and clinical missions.

Letters of inquiry and curriculum vitae as well as the names and addresses of five references should be sent to:

Stefan Heller, PhD – Chair of Basic Science Search Committee

Department of Otolaryngology – Head & Neck Surgery

801 Welch Road, Stanford, CA 94305-5739

sheller@ohns.stanford.edu

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We are proud to announce that the International Congress on Cell Biology will be held for the first time in Latin America. The International Federation for Cell Biology (IFCB) and the Brazilian Society for Cell Biology (SBBC) are working together to host this Meeting in Rio de Janeiro, Brazil, from July 25th through 28th, 2012.
The aim of this Congress is to provide an exciting forum where undergraduate and graduate students, post docs and researchers from around the world can freely discuss about Science, in general, and different aspects of Cell Biology in particular, to start new collaborations and define future trends for cell science and technology. Efforts are underway in putting together a comprehensive and inspiring program broaching at least 30 different topics.

The meeting will be held at Riocentro Exhibition and Convention Center at Avenida Salvador Allende, 6555 – Barra da Tijuca – Rio de Janeiro – RJ – Brazil

The 10th ICCB/16th SBBC Meeting features:
• Plenary lectures, Round Table and Young Investigators sessions with local and international invited speakers
• Concurrent scientific sessions open to all attendees
• Pre-meeting workshops on state-of the art techniques and approaches
• Exhibit booths displaying an array of equipment, supplies and publications from local and international companies
• 2 days of poster sessions

Congress Language:

Because this is an international meeting, all activities will be conducted and sponken in English.

For more information, contact: iccb2012@interevent.com.br

(3 votes)

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Conference season is about to kick off, so here are a few registration dates for various meetings you might want to attend. If you know of any others, please leave a comment below. And of course keep checking the events calendar (and add any events not on there yet – see the help page for instructions on creating accounts and adding events)

January 16 (today!) – early registration deadline for the Sixth International Symposium on Vertebrate Sex Determination. They’re based in Hawaii, so you may still make the early registration deadline.
January 20 – early registration deadline for Drosophila Meeting (final deadline on February 29)
February 8 – registration/abstracts deadline for the 12th International Conference on Limb Development and Regeneration
March 1 – Application deadline for “The Stem Cell Niche – Development and Disease” in Copenhagen (see poster below)
March 23 – Early registration deadline for the BSDB/BSCB/JSDB meeting

To celebrate the opening of the Copenhagen Stem Cell Centre (DanStem), the foundation is hosting a conference from June 25 to 27. If you’re selected as participant, they will cover hotel, registration, local transport and meals. See poster below for speaker list.
(more…)

(2 votes)

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Here are the highlights from the current issue of Development:

CycA takes control of endoreplication

Endocycles – repeated rounds of DNA replication without intervening mitoses – are involved in several terminal differentiation events. In Drosophila, for example, endoreplication occurs during the terminal differentiation of mechanosensory bristles. Endocycles are thought not to involve mitotic cyclins but here (p. 547), Agnès Audibert, Michel Gho and colleagues overturn that view by showing that cyclin A (CycA), which was thought to function exclusively in mitosis in Drosophila, is involved in endoreplication in the bristle lineage. The researchers show that CycA accumulates during the last part of endoreplication. CycA loss- and gain-of-function both induce changes in the dynamics of endoreplication, they report, and reduce the number of endocycles. Finally, CycA is required for relocalisation of ORC2, a member of the pre-replication complex, to the heterochromatin. These and other data reveal that CycA oscillations regulate endocycle dynamics in the fly mechanosensory bristle lineage and suggest that endoreplication involves remodelling of the entire cell-cycle network rather than simply a restriction of the canonical cell cycle as previously suggested.

Plane fact: aPKC orientates mitotic spindles

Mitotic spindle orientation, which is essential for epithelial morphogenesis and tissue maintenance, involves interactions between cortical polarity components and astral microtubules. The molecular machinery that regulates spindle apicobasal orientation during asymmetric cell division is well understood but what orientates the spindle along the epithelial plane in symmetrically dividing epithelial cells? On p. 503, Rui Gonçalo Martinho and colleagues provide the first in vivo evidence that atypical protein kinase C (aPKC) is involved in this process. Using a temperature-sensitive aPKC allele, the researchers show that Drosophila aPKC is required in imaginal discs for spindle planar orientation and for apical exclusion of Pins, a component of the molecular machinery that links the cell cortex to the astral microtubules. Apically localized aPKC is important for spindle planar orientation in mammalian epithelial cells in tissue culture; thus, these new observations suggest that the cortical cues required for spindle planar orientation are conserved between Drosophila and mammalian cells and are similar to those required for spindle orientation during asymmetric cell division.

pecanex wraps Notch up

During early development of the Drosophila nervous system, Notch signalling limits neuroblast numbers by preventing the cells that neighbour neuroblasts from also choosing a neuroblast fate. Disruption of Notch signalling prevents this ‘lateral inhibition’ and produces hyperplasias of the embryonic nervous system. The absence of pecanex (pcx), which encodes a conserved multi-pass transmembrane protein of unknown function, also causes a similar neurogenic phenotype. Now, Kenji Matsuno and colleagues propose that Pcx is a novel component of the Notch signalling pathway in Drosophila (see p. 558). They show that Pcx resides in the endoplasmic reticulum (ER) and is required upstream of activated Notch. Disruption of pcx function, they report, results in ER enlargement. However, hyper-induction of the unfolded protein response in the absence of pcx suppresses both ER enlargement and the development of a neurogenic phenotype. Together, these results suggest that the ER plays a previously unrecognised role in Notch signalling that involves Notch folding and that this ER function depends on pcx activity.

Wnt signalling regulates ciliogenesis

In zebrafish embryos, motile cilia lining the Kupffer’s vesicle (KV; the fish equivalent of the mouse node) help to establish left-right (LR) asymmetry. Wnt/β-catenin signalling is also involved in this process but precisely how it functions is unclear. Xueying Lin and colleagues now reveal that Wnt/β-catenin signalling directly regulates ciliogenesis in the zebrafish KV (see p. 514). The researchers show that reduced Wnt signalling disrupts LR patterning and ciliogenesis and downregulates Foxj1, a transcription factor that is required for the biosynthesis of motile cilia. KV-specific expression of foxj1a, they report, requires the presence of putative Lef1/Tcf binding sites in the foxj1a enhancer region, which suggests that Wnt signalling activates fox1ja transcription directly. Importantly, reduction of Wnt signalling also impairs foxj1 expression and ciliogenesis in developing zebrafish pronephric ducts and otic vesicles, epithelial structures that require Wnt activity for their development and function. The researchers propose, therefore, that the regulation of Foxj1 expression and ciliogenesis by Wnt/β-catenin signalling is a general developmental mechanism in zebrafish.

Egg cell orchestrates gametophyte development

Plant germ cells develop in specialised haploid structures called gametophytes. The female gametophyte of flowering plants contains an egg cell (which develops into the embryo), a central cell (which generates the endosperm that nurtures the embryo) and two accessory cell types, but what coordinates the development of these different cell types? On p. 498, Rita Groß-Hardt and co-workers report that egg-cell signalling mediated by LACHESIS (LIS), which encodes a homologue of a yeast pre-RNA splicing factor, regulates the development of Arabidopsis female gametophytic cells. lis mutants form supernumerary egg cells at the expense of accessory cells. The researchers now show that reducing LIS transcript levels specifically in the egg cell affects all the gametophyte cell types, which suggests that the egg cell orchestrates gametophyte differentiation. Notably, reduced LIS transcript levels in the egg cell interfere with homotypic nuclei fusion in the central cell and, consequently, endosperm formation. Thus, LIS-mediated egg-cell signalling ensures that endosperm only forms in the presence of a functional egg cell.

DAZL takes heat off testes

Mammalian testes are usually located outside the body cavity to ensure that the male germ cells are maintained at a low enough temperature to develop properly. If the testes get too warm, heat stress can cause germ cell apoptosis, which reduces fertility. Now, on p. 568, Kunsoo Rhee and co-workers reveal a cellular mechanism that protects male germ cells from heat stress. The researchers show that brief exposure of mouse testes to the core body temperature induces the assembly of stress granules (SGs; non-membranous cytoplasmic particles that contain translationally inert messenger ribonucleoproteins) in male germ cells. DAZL, a germ cell-specific translational regulator, translocates to SGs upon heat stress, they report, and is essential for their assembly. Importantly, DAZL-containing SGs sequester specific signalling molecules, such as RACK1 (receptor for activated protein kinase C), thereby blocking the apoptotic MAPK pathway. Together, these results suggest that DAZL is an essential component of SGs and that SGs prevent male germ cells from undergoing apoptosis upon heat stress.

Plus…

New for this year: poster articles!

Cilia in vertebrate development and disease

Oh and Katsanis provide a snapshot of the structure, function and distribution of the vertebrate cilium and of the pathologies that are associated with its dysfunction.

See the Development at a Glance poster article on p. 443

A taste of TGFβ in Tuscany

The recent FASEB Summer Research Conference entitled ‘The TGFβ Superfamily: Signaling in Development and Disease’ was held in August, 2011 in the spectacular setting of Il Ciocco, Lucca, amidst the olive trees in Tuscany, Italy. Here, Hata and Brivanlou review this meeting and highlight the recent advances that have been made in our understanding of the transforming growth factor-β (TGFβ) signaling pathway.

See the Meeting Review on p. 449

Regulation of DNA replication during development

During development, DNA replication is coordinated with cell proliferation and is regulated uniquely in specific cell types and organs. Here, Nordman and Orr-Weaver highlight recent advances and technologies that have provided us with new insights into the developmental regulation of DNA replication.

See the Review on p. 455

(1 votes)

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Our intestinal tissue doesn’t need a New Year’s resolution to keep up its amazing productivity.  Our intestinal epithelium is replenished at breakneck speed in an assembly line that begins with stem cells.  Today’s image is from a recent Development paper that discusses the importance of Notch signaling in stem cell self-renewal and intestinal homeostasis.

Our intestinal epithelium is folded and shaped into finger-like villi (“shaggy hair” in Latin) that increase the surface area of the tissue for more nutrient absorption.  Each villus has several populations of cells in homeostasis in order to maintain function and constant replenishment.  This production of epithelium starts with the actively-dividing crypt base columnar (CBC) stem cells that sit in the crypts.  Although the identity of these cells has been known for a while, the factors regulating CBC stem cell self-renewal and differentiation were not well understood.  A recent Development paper discusses the role for Notch signaling in CBC stem cell function.  According to VanDussen and colleagues, Notch signaling is required for CBC stem cell self-renewal and survival.  Notch inhibition caused a decrease in the number CBC cells, as well as precocious differentiation of more specialized intestinal cell types.  VanDussen and colleagues showed that Notch regulates CBC cell self-renewal and cell fate choice through different pathways and by targeting different cell populations.  In the images above, intestinal tissue was stained for a marker of CBC stem cells (Lgr5, green) and for proliferating cells (Ki67, red).  In normal tissue (left), CBC stem cells were found at the base of the crypts, some of which were also actively dividing (arrows).  Notch inhibition (right) resulted in a misshapen morphology of CBC stem cells, a decrease in the CBC cell marker, and a drop in the number of CBC cells that were actively dividing (arrowheads on left).

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

VanDussen, K., Carulli, A., Keeley, T., Patel, S., Puthoff, B., Magness, S., Tran, I., Maillard, I., Siebel, C., Kolterud, A., Grosse, A., Gumucio, D., Ernst, S., Tsai, Y., Dempsey, P., & Samuelson, L. (2011). Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells Development, 139 (3), 488-497 DOI: 10.1242/dev.070763

(3 votes)

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The Company of  Biologists run 3 cutting edge Workshops each year organised by the leading scientists in their fields.   They are small workshops with 30 attendees made up of 20 invited speakers and 10 places for early career scientists. The Workshops this year are;

New Technologies and Applications for Genome Engineering – 25th – 28th March 2012 – UK

Epigenetic Memory – 24th – 27th June 2012 – UK

Imaging in Cell Biology: Where next? – 14th – 17th October 2012 – UK

If you are a student, postdoc or in your first PI position and are interested in attending any of the Workshops detailed above, please contact workshops@biologists.com.  The deadline for applications for the March Workshop is the 21st January.  For more information please see our website – http://workshops.biologists.com.

(2 votes)

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Somites, confocal, epigenetics, germline, stem cell… BINGO!

Thanks to all of your help and suggestions, BenchFly has now produced the Developmental Biology Group Meeting Bingo game.

From their post:

“Bingo? Are we actually suggesting you gamble during seminars? Yes! No. We’re simply providing a few key words that you may listen for during a talk… and if it just so happens that your card yields “Bingo!” sooner than your labmates’ and they have to take you out to lunch as a result, so be it…”

Visit BenchFly to play the game. You can refresh the card to get individual ones. There are over a hundred words, so there are many different possible cards to get. Good luck!

(3 votes)

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