Shruti Vemaraju¹ and Richard A. Lang¹-² 

¹Center for Chronobiology,¹The Visual Systems Group, Abrahamson Pediatric Eye Institute, Division of Pediatric Ophthalmology, ²Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA. ²Department of Ophthalmology, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA

We live on a planet that is close to a yellow dwarf star. This means that throughout the evolution of life, photons have been available. Living systems have exploited photon availability for adaptive advantage using pathways like photosynthesis, the circadian clock and the visual system. However, in addition to these obvious examples, we are learning that metazoans can decode light information in other ways. Here we comment on recent work from the Lang lab that describes how light signals can provide developmental timing cues. 

The embryonic eye has an elaborate vessel network, called the hyaloid vasculature, that supplies nutrients and oxygen to the developing retina. This network is transient and undergoes programmed regression concomitantly with the development of retinal vasculature. Regression of the hyaloid vessels is an adaptation for high acuity vision: Since the structure lies in the optical path and would scatter light, its regression is necessary for optical function of the eye. The clinical conditions persistent fetal vasculature (PFV) and persistent hyperplastic primary vitreous (PHPV) are a consequence of abnormal hyaloid vessel regression.   

Research in the Lang lab has focused on development of vasculature in the eye since 1993 when we showed that myeloid cells play an important role in scheduled vascular regression (Lang and Bishop, 1993). The molecular pathways required for hyaloid vessel regression (the Wnt, Angiopoietin and VEGF pathways) have been defined by our group and by several others (Gale et al., 2002; Glass II et al., 2005; Kurihara et al.; Liu and Nathans, 2008; Lobov et al., 2002; Nayak et al., 2018; Rao et al., 2007; Yoshikawa et al., 2016). The hyaloid vessel system is an interesting subject of study in part because it can be dissected from the eye as a whole mount and the vessels easily counted. The hyaloid vasculature may seem like an obscure structure (it is) but has featured on the front cover of Development twice (Nayak et al., 2018; Rao et al., 2007)(Fig. 1). 

Despite all that had been learned, the trigger that initiated hyaloid regression remained to be elucidated. When the Lang lab considered this question, we thought about the possibility that light stimulation could be the trigger. After all, this was an eye, a structure designed to respond to light, and hyaloid vessel regression began soon after birth when light exposure levels would presumably be elevated. To investigate this initially, we (that is, Lang Lab alumnus Sujata Rao) dark-reared mice and found hyaloid vessel persistence, an indication that light stimulation could be involved. 

What unfurled next was a nice illustration of how science investigations sometimes work. Our colleague Maureen McCall was visiting from Louisville and, after she heard about our work, recommended we contact David Copenhagen (UCSF) because he was also working on light response pathways in neonatal mice. Excited by the possibilities, we contacted David and learned that newborn mice have a negative phototaxis (a light aversion response) mediated by melanopsin (OPN4), one of the non-canonical retinal opsins (Johnson et al., 2010). This raised the possibility that melanopsin might also regulate hyaloid regression and sure enough, when Sujata assessed Opn4 null mice, we found hyaloid vessel persistence (thanks for the hot tip Maureen). Subsequently, the Lang and Copenhagen labs worked together to understand how melanopsin controlled the timing of vascular regression. 

Key findings included the observation that dark reared and Opn4 null mice developed an over-abundance of retinal neurons, showed elevated oxygen demand and elevated levels of vascular endothelial growth factor A (VEGFA), a crucial promoter of angiogenesis and vascular endothelial cell survival (Rao et al., 2013). Elevated levels of VEGFA provided a good explanation for the promiscuous retinal angiogenesis and hyaloid vessel persistence characteristic of the Opn4 null and dark-reared mice (Rao et al., 2013). In a little bit of a surprise, the analysis suggested that the light-OPN4 pathway functioned before birth in a fetal eye that was directly light responsive. While some of our colleagues have struggled with the idea that deep tissue photoreceptors can receive sufficient light to function, there is evidence throughout the animal kingdom that this is one mode of light detection (Miyashita et al., 1996; Nakane et al., 2010; Okano et al., 1994) and recent analysis from the Lang and Copenhagen labs confirms that this is the way this pathway works (stay tuned….). 

Prompted by this work, the Lang lab become much more curious about the possibility that other light response pathways could play an important role in development. Genome sequencing nearly two decades earlier had identified two other non-canonical opsins, neuropsin (OPN5, (Tarttelin et al., 2003)) and encephalopsin (OPN3, (Blackshaw and Snyder, 1999)). Both of these were expressed in the retina and so as a first assessment, the Lang lab determined whether a null mouse for either opsin has a vascular phenotype in the eye: In Opn5 null mice, we found one (Nguyen et al., 2019).

The Lang lab has trained a small cadre of researchers to perform hyaloid vessel dissections (the dissection requires steady hands, patience, specialized technique, and freshly harvested eyes). On the day we first analyzed the Opn5 mouse hyaloid vessels, we had three litters all at the same stage of development. This meant a long day of dissections for Postdoc Shruti Vemaraju (50 eyes and about 6 hours of dissection) in which she was blinded to the genotype and so had no idea of the outcome as she worked. After all the staining and counting was complete, we were excited to learn that loss of OPN5 function resulted in precocious hyaloid vessel regression (Nguyen et al., 2019). This was unusual because all hyaloid phenotypes described to date showed vessel persistence (Fig. 2). OPN5 is known to be stimulated by violet light with peak absorbance at 380 nm (Kojima et al., 2011). Withdrawing this wavelength during the neonatal period mimicked the precocious hyaloid vessel regression seen with loss of OPN5 function (Nguyen et al., 2019). This made a strong argument that OPN5 was functioning as an opsin to regulate hyaloid regression.

So, to summarize, we now knew that two distinct opsins, OPN4 and OPN5 each regulated hyaloid vessel regression, but because the phenotypes were opposite, probably used distinct mechanisms. We knew from prior work (a collaboration with the labs of Russell Van Gelder, King-Wai Yau and Ethan Buhr) that Opn5 was expressed in retinal ganglion cells (RGCs)(Buhr et al., 2015). Since we had not been able to identify any antibodies that detected OPN5, we generated an Opn5cre allele as a means of targeting and characterizing Opn5 RGCs. Conversion of the Ai14 tdTomato cre reporter confirmed that positive cells had all the characteristics of RGCs (Fig. 3) including projections to the lateral geniculate nucleus and superior colliculus.

When Lang lab Research Associate Minh-Thanh Nguyen was characterizing the Opn5 null retina, she noticed an unusual pattern of expression of tyrosine hydroxylase, the rate limiting enzyme in the pathway that synthesizes dopamine. This suggested that dopamine might be changed and, according to an ELISA assessment, it was low in retinal neurons and high in the extracellular vitreous (where the hyaloid vessels reside). This was interesting because dopamine can have an anti-vascular function: via the dopamine receptor DRD2, dopamine can activate the phosphatase Shp2 and promote dephosphorylation of VEGF receptor 2 (Sinha et al., 2009). This suggested the hypothesis that an OPN5 light response pathway regulated hyaloid vessel regression using dopamine as a signaling intermediate. 

Aided by dopamine expert and collaborator Mike Iuvone at Emory University, we investigated this idea further and showed that hyaloid regression could be both positively (precocious regression with receptor agonists) and negatively (vessel persistence with receptor antagonists) regulated by dopamine signaling. We further showed that a key regulator of dopamine uptake, the dopamine transporter (DAT) was activated (via phosphorylation (Foster et al., 2012) by 380 nm light in an Opn5-dependent manner. Phospho-DAT was detected in a network of neuronal processes throughout the inner retina and so was well placed to globally regulate dopamine levels. Using a pharmacological inhibitor of DAT, we could revert hyaloid vessel persistence resulting from dark-rearing to normal numbers and also reproduce an Opn5 null precocious hyaloid vessel phenotype in Opn5 heterozygote mice. These findings led to the hypothesis that hyaloid vessel regression is regulated by an intricate balance between dopamine and VEGFA signaling.  

The hypothesis that dopamine was a signaling intermediate also required that hyaloid vascular endothelial cells (VECs) expressed a dopamine receptor. We detected DRD2 in the hyaloid vessels by immunolabeling and further showed that conditional deletion of a Drd2 floxed allele in VECs resulted in hyaloid persistence. When combined with Opn5 loss-of-function (elevated dopamine levels in vitreous, precocious regression), deletion of Drd2 from VECs abrogates the effects of dopamine signaling and restores hyaloid vessel numbers to normal. This was consistent with a direct effect of dopamine promoting hyaloid vessel regression.  

A further prediction of the hypothesis was that VEGFR2 signaling in the hyaloid vessels would be influenced by dopamine. To test this, Lang lab Postdoc Yoshinobu Odaka performed immunoblotting on the vanishingly small quantities of cell lysates available from hyaloid vessel preparations. He assessed the levels of total and phospho–tyrosine 1173-VEGFR2 (an activating modification) in control and Drd2 VEC conditional deletion hyaloids. Consistent with the hypothesis, pY1173-VEGFR2 was elevated when Drd2 was deleted. This supported the idea that normally DA signaling suppresses VEGFR2 and provided a mechanistic explanation for how the high levels of vitreal dopamine in the Opn5 null could promote precocious hyaloid vessel regression.

During review of the manuscript describing this work, we were asked quite a few questions about how the OPN4 and OPN5 vascular pathways were integrated. The schematic (Fig. 4) describes our current model. We propose that blue light photons activate OPN4 before birth. Through a mechanism not currently understood, this suppresses the number of retinal neurons that develop. When mice are dark–reared or have OPN4 loss-of-function, cellularity and oxygen demand are higher, and this stimulates production of VEGFA. Under those abnormal conditions, VEGFA within the retina produces promiscuous angiogenesis while vitreal VEGFA suppresses regression of the hyaloid vessels. This means that normally, blue light stimulation of fetal retina suppresses the levels of VEGFA as a prerequisite for regression of the hyaloid vessels. 

Current analysis suggests that OPN5 functions after birth to suppress the level of vitreal dopamine. This dopamine suppresses VEGFR2 signaling and promotes hyaloid vessel regression. However, this occurs when dopamine levels in the eye are generally rising because the TH+ amacrine cells that are the source of dopamine are differentiating and becoming active. This series of positive and negative influences means that the net effect of violet light and OPN5 activity is to sustain the hyaloid vessels. This mechanism likely evolved to ensure that hyaloid vessel regression does not occur before the first layer of retinal vasculature is complete: this would prevent hypoxia by ensuring that one of the vascular networks was always functional. One way to think about OPN4 and OPN5 function in the developing eye is that they are the detectors for developmental timing cues. A reminder that in development, timing is everything. 

References 

Blackshaw, S. and Snyder, S. H. (1999). Encephalopsin: a novel mammalian extraretinal opsin discretely localized in the brain. J Neurosci 19, 3681–3690. 

Buhr, E. D., Yue, W. W., Ren, X., Jiang, Z., Liao, H. W., Mei, X., Vemaraju, S., Nguyen, M. T., Reed, R. R., Lang, R. A., et al. (2015). Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea. Proc Natl Acad Sci U S A 112, 13093–13098. 

Foster, J. D., Yang, J. W., Moritz, A. E., ChallaSivaKanaka, S., Smith, M. A., Holy, M., Wilebski, K., Sitte, H. H. and Vaughan, R. A. (2012). Dopamine transporter phosphorylation site threonine 53 regulates substrate reuptake and amphetamine-stimulated efflux. J. Biol. Chem. 287, 29702–29712. 

Gale, N. W., Thurston, G., Hackett, S. F., Renard, R., Wang, Q., McClain, J., Martin, C., Witte, L., Witte, M. H., Jackson, D., et al. (2002). Angiopoietin-2 is Required for Postnatal Angiogenesis and Lymphatic Patterning, and Only the Latter is Rescued by Angiopoietin-1. Dev Cell 3, 411–423. 

Glass II, D. A., Bialek, P., Ahn, J. D., Starbuck, M., Patel, M. S., Clevers, H., Taketo, M. M., Long, F., McMahon, A. P., Lang, R. A., et al. (2005). Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev. Cell 8,. 

Johnson, J., Wu, V., Donovan, M., Majumdar, S., Renteria, R. C., Porco, T., Van Gelder, R. N. and Copenhagen, D. R. (2010). Melanopsin-dependent light avoidance in neonatal mice. Proc Natl Acad Sci U S A 107, 17374–17378. 

Kojima, D., Mori, S., Torii, M., Wada, A., Morishita, R. and Fukada, Y. (2011). UV-sensitive photoreceptor protein OPN5 in humans and mice. PLoS One 6, e26388. 

Kurihara, T., Kubota, Y., Ozawa, Y., Takubo, K., Noda, K., Simon, M. C., Johnson, R. S., Suematsu, M., Tsubota, K., Ishida, S., et al. von Hippel-Lindau protein regulates transition from the fetal to the adult circulatory system in retina. Development 137, 1563–1571. 

Lang, R. A. and Bishop, J. M. (1993). Macrophages are required for cell death and tissue remodeling in the developing mouse eye. Cell 74,. 

Liu, C. and Nathans, J. (2008). An essential role for frizzled 5 in mammalian ocular development. Development 135, 3567–76. 

Lobov, I. B., Brooks, P. C. and Lang, R. A. (2002). Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. PNAS 99, 11205–11210. 

Miyashita, Y., Moriya, T., Yokosawa, N., Hatta, S., Arai, J., Kusunoki, S., Toratani, S., Yokosawa, H., Fujii, N. and Asami, K. (1996). Light-sensitive response in melanophores of Xenopus laevis: II.Rho is involved in light-induced melanin aggregation. J. Exp. Zool. 276, 125–31. 

Nakane, Y., Ikegami, K., Ono, H., Yamamoto, N., Yoshida, S., Hirunagi, K., Ebihara, S., Kubo, Y. and Yoshimura, T. (2010). A mammalian neural tissue opsin (Opsin 5) is a deep brain photoreceptor in birds. Proc. Natl. Acad. Sci. 107, 15264–15268. 

Nayak, G., Odaka, Y., Prasad, V., Solano, A. F., Yeo, E.-J., Vemaraju, S., Molkentin, J. D., Trumpp, A., Williams, B., Rao, S., et al. (2018). Developmental vascular regression is regulated by a Wnt/β-catenin, MYC and CDKN1A pathway that controls cell proliferation and cell death. Development 145, dev154898. 

Nguyen, M.-T., Vemaraju, S., Nayak, G., Odaka, Y., Buhr, E. D., Alonzo, N., Tran, U., Batie, M., Upton, B. A., Darvas, M., et al. (2019). An Opsin 5-dopamine pathway mediates light-dependent vascular development in the eye. Nat. Cell Biol. In press,. 

Okano, T., Yoshizawa, T. and Fukada, Y. (1994). Pinopsin is a chicken pineal photoreceptive molecule. Nature 372, 94–7. 

Rao, S., Lobov, I. B., Vallance, J. E., Tsujikawa, K., Shiojima, I., Akunuru, S., Walsh, K., Benjamin, L. E. and Lang, R. A. (2007). Obligatory participation of macrophages in an angiopoietin 2-mediated cell death switch. Development 134,. 

Rao, S., Chun, C., Fan, J., Kofron, J. M., Yang, M. B., Hegde, R. S., Ferrara, N., Copenhagen, D. R. and Lang, R. A. (2013). A direct and melanopsin-dependent fetal light response regulates mouse eye development. Nature 494, 243–246. 

Sinha, S., Vohra, P. K., Bhattacharya, R., Dutta, S., Sinha, S. and Mukhopadhyay, D. (2009). Dopamine regulates phosphorylation of VEGF receptor 2 by engaging Src-homology-2-domain-containing protein tyrosine phosphatase 2. J Cell Sci 122, 3385–3392. 

Tarttelin, E. E., Bellingham, J., Hankins, M. W., Foster, R. G. and Lucas, R. J. (2003). Neuropsin (Opn5): a novel opsin identified in mammalian neural tissue. FEBS Lett 554, 410–416. 

Yoshikawa, Y., Yamada, T., Tai-Nagara, I., Okabe, K., Kitagawa, Y., Ema, M. and Kubota, Y. (2016). Developmental regression of hyaloid vasculature is triggered by neurons. J. Exp. Med. 213, 1175–1183. 

 

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In the context of a multidisciplinary study funded by an ERC advanced grant, the Milinkovitch lab offers one position for an outstanding, highly motivated, and creative experimental wet-lab biologist or biophysicist (at the Post-doc level or, possibly, PhD student level) with strong skills in Cell and Developmental Biology as well as experience in Biophysics. The position is for 3 to 5 years and must start between September and December 2019. The successful candidate will use molecular/cell/developmental biology and biophysics methods to investigate (i) how cell proliferation and tissue differentiation are coupled to mechanical tension during scale development in reptiles and birds, and (ii) how geometry of the skin affects reaction diffusion during the development of skin colour patterns in reptiles. These analyses will be performed on new model species (lizards, snakes, crocodiles, birds) already established in the Milinkovitch lab.

Excellent written and verbal communication skills in

English are mandatory. Other specific requirements are strong expertise in

• Cell and Developmental Biology: CRISPR-Cas9 technology, ex-vivo tissue cultures, confocal and light-sheet microscopy, immuno-histochemistry, in-situ hybridisation, transcriptomics, in-vivo assays;
• Biophysics: micro-indentation, physical experiments with PDMS/hydrogels, laser ablations, etc.

Candidates must have a PhD in Biology or biochemistry or Biophysics. The position is available at the level of Post-Doc / Research Associate. Exceptional master students can be considered for a PhD student position. 

The University of Geneva (UNIGE) is world-renowned for its research and is among the top 1% best universities in the world. Geneva is an international city occupying a privileged geographical situation.

Candidates must send their application — in the form of a single PDF file including a brief letter of interest, a CV, as well as contact information (not support letters) of three persons of reference — to: lane-jobs@unige.ch 

Deadline for application: July 15, 2019.

References
: Elastic instability during branchial ectoderm development causes folding of the Chlamydosaurus erectile frill.
eLIFE (in press). Locally-curved geometry generates bending cracks in the African elephant skin. Nature Communications 9 (2018); A Living
Mesoscopic Cellular Automaton Made of Skin Scales. Nature 544: 173-179 (2017); The Anatomical Placode in Reptile Scale Morphogenesis Indicates Shared Ancestry Among Skin Appendages in Amniotes. Science Advances 2, 6: e1600708 (2016); Photonic Crystals Cause Active Colour Change in Chameleons. Nature Communications 6: 6368 (2015); The genome sequence of the corn snake (Pantherophis guttatus). Int. J. Dev. Biol. 58 : 881 – 888 (2014); Crocodile Head Scales Are Not Developmental Units But Emerge from Physical Cracking. Science 339, 78-81 (2013). Crocodylians Evolved Scattered Multi-Sensory Micro-Organs. EvoDevo 2013, 4:19.

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James Briscoe is a Group leader at the Francis Crick Institute in London, where he and his lab work on the development of the spinal chord using both molecular biology and mathematical modeling approaches. In this Podcast we talk about his science as well as the future directions he would like to take as the editor-in-chief of the journal “Development”. We hope you enjoy listening!

DanStem podcast team

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Postdoc Position: Visible Ape & Dissemination

Hiring Institution: Howard Univ.; Posted: 06-11-2019; Duration PostDoc: Sept2019-Aug2022

A postdoctoral researcher is sought to join the Rui Diogo lab (www.ruidiogolab.com), at the Howard University College of Medicine, Department of Anatomy (Washington DC).

Within the field, this is one of the labs with a higher impact, number of publications in top journals, books, awards, and press coverage (TV, newspapers, press releases, etc.). Therefore we are looking for someone that is not only a relatively independent, top researcher, but also highly motivated, ambitious, willing to learn, and to help in dissemination – a crucial component of the philosophy of the laboratory-, including travels to rural communities in Africa and several scientific meetings. On the other hand, this means the researcher will gain a huge experience and be part of several top publications, therefore becoming highly prepared for a more senior position, after those 3 years, as has been the case with the vast majority of our previous postdocs. See also:
Researchgate: https://www.researchgate.net/profile/Rui_Diogo
Diogo Lab’s books: http://www.amazon.com/Rui-Diogo/e/B001JS2K96

We are therefore interested in a candidate that will have the ability to:

1) Help to coordinate a major, NSF-funded project to produce a Visible Ape Website and mobile app that is similar to, and will be directly compared with, the Visible Human Project.

2) Help write review papers and books on broader evolutionary topics, therefore getting a substantial experience in publishing in top journals and monographs.

3) Have the willingness to disseminate science and bring awareness to ape conservation, including in rural communities in Africa, DC public schools, scientific meetings, and numerous other places. Therefore, the researcher should have a good, and ideally a very good, English level, as well as writing skills.

4) Have a high independence, and the drive to be highly productive, taking advantage of the broader scope and numerous collaborations of the lab, while also enjoying a vast liberty, concerning both a daily-basis schedule and at an intellectual level.

Interested candidates should send a 1-page letter addressing this announcement, as well as a detailed CV 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 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 Smithsonian Institution, and the candidate will probably have the opportunity to do part of his/her research at those institutions and thus to further expand his/her knowledge and academic connections.

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Highly motivated postdoctoral candidates are invited to lead several new projects to address fundamental questions in protein and RNA homeostasis related to neurodegenerative diseases in the laboratory of Jiou Wang. Experimental approaches, including biochemistry, genetics, and cell biology, from invertebrate to mammalian systems are employed. New techniques applied in the lab include iPSC neurons, genome editing, single cell analysis, and metabolite studies. Candidates with a strong background in biochemical, molecular, and/or cellular biology are encouraged to apply.

The Johns Hopkins Medical Institutions provide a stimulating and collaborative environment for biomedical research. Our lab is affiliated with the Department of Biochemistry and Molecular Biology at the Bloomberg School of Public Health and the Department of Neuroscience at the School of Medicine. The Baltimore/Washington D.C. area also offers rich professional and living opportunities.

Candidates should have a doctoral degree and strong research background. Please send a statement of research experience and career goals, a copy of Curriculum Vitae, and contact information of at least one reference to Dr. Jiou Wang at jiouw@jhmi.edu.

A complete listing of PubMed-accessible publications can be accessed at the following URL: http://www.ncbi.nlm.nih.gov/pubmed/?term=Jiou+Wang.

More information available at: https://www.jhsph.edu/faculty/directory/profile/2251/jiou-wang.The Johns Hopkins University is an Equal Opportunity Employer.

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 In this episode of Genetics Unzipped, reporter Graihagh Jackson loses herself in the valley of hybridisation, visiting the Society’s medal-winning Mendel-based garden at the RHS Chelsea Flower Show and speaking with Professor Wendy Bickmore (MRC HGU, Edinburgh) and Dr Greg Mellers (NIAB, Cambridge). Plus, Professor Laurence Hurst (University of Bath) on the importance of playing with your genes.

Listen and download now from GeneticsUnzipped.com, plus full show notes and transcripts.

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Press release from Development. You can also read the Research Highlight for this article.

Alcohol consumption during pregnancy has been linked to poor growth of the placenta, causing conditions such as fetal growth restriction and low birth weight. Although most women cease drinking once they know they are pregnant, the effect of alcohol during the initial stages of pregnancy, even as early as around the time of conception, is less well understood. Now, Dr Jacinta Kalisch-Smith together with Professor Karen Moritz at the University of Queensland in Australia have investigated the impact of alcohol consumption on the placenta early in pregnancy. They show that the growth of the placentas of rats that consumed alcohol around the time of conception was reduced significantly, providing new evidence for how pregnancy-related conditions develop. This research has just been published in the scientific journal Development.
“We wanted to know whether early alcohol exposure could affect the development of the early embryo and the placenta. Using a rat model, we assessed the ability of the embryo to implant into the uterus, and, later, how well blood vessels formed in the placenta,” explained Kalisch-Smith.

Using this approach, the scientists were able to study changes that happen throughout the rat’s pregnancy and found that even early exposure to alcohol (between 4 days before and 4 days after fertilisation) restricted the growth and function of the placenta.

“We found early alcohol exposure reduced blood vessel formation in the placenta, and this led to fewer nutrients being delivered to the embryo,” said Kalisch-Smith.

Strikingly, the placentas of female embryos were particularly susceptible, with up to a 17% reduction in size and a 32% drop in blood vessel formation, limiting the ability of the placenta to transport nutrients.

“This has implications for human health by helping to explain, in part, why babies exposed to alcohol in the womb are often born small,” said Kalisch-Smith. “It is important to understand the causes of low birth weight, because it has been shown to be an independent risk factor for diseases later in adulthood, such as type 2 diabetes, hypertension and obesity.”

These observations provide an important basis for future research into pregnancy-associated conditions like fetal growth restriction. Kalisch-Smith added, “The next part of this project is to see whether nutrient supplementation can reduce or even prevent the adverse effects of alcohol exposure.”

The full study, “Periconceptional alcohol exposure causes female-specific perturbations to trophoblast differentiation and placental formation in the rat” appears in the journal, Development.

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Here we hear the experiences of three students who completed a developmental biology course in Zhiyuan College in Shanghai, as well as an introduction to the course by organiser Guojun Sheng

Zhiyuan College (https://zhiyuan.sjtu.edu.cn/articles/701) of Shanghai Jiao Tong University (STJU) is an undergraduate talent-training program founded by then president Zhang Jie in 2010. Its philosophy is to place a small group of selected students in a non-traditional learning environment so that they can explore their genuine academic interest and realize their full intellectual potentials. Each year, Zhiyuan College recruits about 20-30 students majoring in Biological Sciences (other majors include Mathematics, Chemistry, Physics, Computer Sciences, Engineering and Biomedical Sciences). Developmental Biology is an elective course offered to all second- and third-year Zhiyuan students, with a usual class-size of 7-15.

The course organizer(s) decides the topics to be covered and invite colleagues who share their passion for developmental biology research and training to teach at Zhiyuan for 1-2 weeks each. Lecturers for this year’s animal development include Drs. Jeremy Green, Shigeo Hayashi, Antoon Moorman, Olivier Pourquie, Fengwei Yu, Weimin Zhong and myself (The course also includes ongoing plant development lectures organized by Prof. Wanqi Liang). Lectures are divided into class-room style teaching (2/3) and journal-club style presentation and discussion (1/3). For most students, this course is the first instance when they get a systematic introduction to developmental phenomena and concepts which had fascinated many of us before we chose developmental biology as a career. Thanks to the small class size and enthusiastic lecturers, students get an early peek into developmental wonders. Each year, after the course, a couple of students kindle their inner passion and pursue further training and education in developmental biology.

Student experiences

Why I study developmental biology

Xinyu Wang

Before I took the course, I considered developmental biology to be just about how a fertilized zygote becomes a baby through cell division and cell differentiation. But when I truly got into it, I found this was quite a shallow representation of the subject, and that there was lots of charm in development.

From the conservation of Hox genes from sea urchin to human, we see the great power of evolution. From the dynamic process of gastrulation, we see the elegant design of the body plan. From the grafting experiments of the Spemann organizer, we see another opportunity of regeneration. All of these impressive scenes greatly broadened my view of developmental biology.

Besides these interesting parts, the idea of interdisciplinary experiments also attracts me. Development is the final result, but the access to get this result is variable. We can see through the egg shell to know how chicken embryos form. We can use forward and reverse genetics to study the important molecules in AP axis formation. We also can utilize bioinformatics strategies to screen homologous genes in different organisms.

The journey of studying developmental biology is far from terminal, and the insight that organisms give will encourage me to work hard in biology.

What I learnt in developmental biology

Yankun Li

This semester we took a course on animal developmental biology for animals and I learnt a lot. Here are some of my feelings on this course.

Arranged in order, there are 7 professors teaching this course in turn. Prof. Sheng was the first to come. He introduced the whole view and outlook of developmental biology, as well as some basic concepts on early embryo development, such as gastrulation. Then, Prof. Zhong came, who was charged with the early development of the nervous system. What impressed me most was the way that he induced and brightened our mind on the topics, though he was somewhat strict. During Prof. Moorman’s stay, I received knowledge not only in academic but also in other aspects. Firstly, I can visualize the cardiac development through his heart model. What’s more, in the seminar, he told us about 3D reconstruction of human embryo. What a fantastic technology that can convert 2D pictures to a 3D model! Besides, the wide conversation between us made it clearer for me how scientists thought about questions. I enjoyed Prof. Hayashi’s lectures very much, by the end of which I knew more about cell-cell junctions. However, I did not do such a good job in the mid-term exam. A-week-long stay might be a little bit short for Prof. Hayashi, because I thought that he still had something to share with us and I retained some questions to ask him, unfortunately, not in time. Prof. Yu told us something about Drosophila and some experiences in the lab. Then Prof. Pourquie came to teach us in the middle of April: his movies gave a better understand on Hox genes. Finally, Prof. Green visited our campus. He is a talkative British with an appealing accent. His lectures were lively and he made the process of morphogenesis concrete in details by comparison, etc. Besides, I appreciated that he taught us how to use a confocal microscope.

Finally, I must say that each professor’s efforts are very respectable. They did their best to teach us the experiences they have got from their lives in research, and so lightened the future of our own scientific research. Thank you all for the cheering lectures. I will never forget the precious knowledge you told us.

Before and after taking the course

Yangye Zhang

The initial reasons why I chose to take the developmental biology course was to fulfill my credit requirements as well as equip myself with more knowledge. Actually, at that time, I had no idea which field in biology I should choose for my further study, so I decided to try as much as I can. Luckily, I met with the one I am willing to devote myself to.

I could still remember the first lecture, which contained lots of movies showing the early embryonic development of Drosophila, Xenopus, birds and mice. I was impressed with these well-organized processes. The more we looked into the detail, the less we knew and the more it attracted me. Later, there were other professors coming to show us certain system development. During that period of time, I learnt lots of experimental techniques to see or test gene expression as well as the way to logically analyze the pathways and links during development. Besides, we also learnt the backgrounds of ESCs and iPSCs, which are good materials to test our hypothesis and reconstruct organs in vitro. Although some parts were a little bit difficult to me, e.g. imaging the 3D gastrulation, I never thought of giving up or felt discouraged. In contrary, I grew strong ambition to figure them out. At that time, I set my dream as being a developmental biologist.

This year, I offered to be the teaching assistant of this course. Although I knew there would not be many students who become real developmental biologists in the future, the way of critical thinking and other information learnt from the course can also benefit us a lot in other fields. I liked it so much and I would like to recommend others to learn developmental biology as well.

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Do you want to share your experience of learning or teaching developmental biology? We’d love to hear from you!

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A PhD position is available in the laboratory of Néva P. Meyer at Clark University in Worcester, MA USA (https://wordpress.clarku.edu/nmeyer/) beginning as early as August 2019 as follows:

Spiralians are a great group of animals to study evolution of body plans in part because many spiralian taxa develop via a stereotypic and likely ancestral cleavage program. Ultimately, this cleavage program results in formation of highly diverse body plans with diverse arrangements of nervous systems, e.g. compare annelids and gastropod mollusks. Research in Dr. Meyer’s lab is currently focused on understanding how the central nervous system develops in annelids with the goal of gaining a better understanding of how nervous systems evolved. The research community that studies evolution and development of spiralians is rapidly growing and is very welcoming and collaborative.

The successful applicant will develop a project focused on molecular control of neural fate specification inthe annelid Capitella teleta, but this can be expanded to include other spiralians and different avenues ofresearch depending on the applicant’s interests and goals. Possible avenues of research include analysisof fate specification via blastomere isolation, genetic manipulation, and transcriptomic profiling. We havea lab colony of Capitella teleta, and techniques used in the lab include microinjection of embryos, qRTPCR, immunohistochemistry, imaging of live and fixed tissue, quantification of phenotypes using ImageJ,and gene knockdown and misexpression by injection of morpholinos and mRNA. We are also currentlydeveloping CRISPR/Cas9 gene editing and single-cell RNA sequencing in C. teleta. There will be multipleopportunities for career development, including mentoring undergraduate and accelerated M.S. studentsin the lab, participating as a guest lecturer in courses taught by the PI, and attending national workshopssuch as the Embryology course at the Marine Biological Laboratories.

The successful applicant will enter Clark University’s Biology PhD program with an anticipated start datein late August. Previous experience in molecular biology and working with marine larvae and/orbioinformatics is desirable. Additionally, the Meyer lab is interested in creative, engaged applicants whocan contribute to diversity of the academic community, for example via outreach or mentoring studentsfrom historically underrepresented communities. The successful applicant will be guaranteed funding forfive years through a combination of research assistantships and teaching assistantships; two years ofresearch assistantship for this position are currently available.

Clark University is a small but active and highly-respected research university located in Worcester, MA.Worcester has a good combination of urban and outdoor activities and is in close proximity to a variety ofNew England destinations.

Please email a cover letter explaining your interest in the position and qualifications and a CV to nmeyer@clarku.edu

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