Ideally you are already providing hands-on, inquiry-based science experiments, which are known to increase achievement and engagement. [Shameless plug: This is something that a zebrafish program that I work with, BioEYES, does well, so if you need help see our website (www.bioeyes.org), our latest research paper in PLOS Biology that details our results and how to launch an outreach program in your area, read our Node post from 2010, or contact me directly.] How engaged are your students? Are there some that are struggling, or who aren’t that committed? Do your lessons speak to the diversity of individuals that you are teaching? Are they culturally relevant?

What does this mean, exactly? Culturally relevant teaching was first described in 1994 by Gloria Ladson-Billings, an education researcher, to mean: “a pedagogy that empowers students intellectually, socially, emotionally, and politically by using cultural referents to impart knowledge, skills, and attitudes.” She suggests reframing how we think about and teach students, especially those typically marginalized by the greater society, from a place of need or as a problem to be fixed, to a place that acknowledges the cultural richness and the assets they bring into the classroom and society.

Culturally relevant teaching is based on the following principles: Academic success, cultural competence, and sociopolitical consciousness (Ladson-Billings, 1994). The first principle, academic success, is that we want learners to grow, intellectually. While seemingly obvious, the unconscious biases we educators harbor can sabotage our best intentions. For example, research shows that we call on “poor” performers less often, and spend less time waiting for them to answer. The second principle, cultural competence, is that we introduce students to the global perspectives found in the greater scientific community and the world. Students can then celebrate not only their own cultures, but learn new perspectives as well. And the third and final principal, sociopolitical consciousness, involves helping students to apply their learning to solving some of the world’s pressing problems.

How does a scientist apply these principles in a science classroom? Let’s first look more closely at what a culturally relevant classroom is like.

• You get to know your students on a meaningful level. You identify what each student is interested in, what their values are, what their home life is like, their traditions, style of communicating, and how they relate to their community.
• You demonstrate caring. By getting to know your students and what they value, you begin to develop meaningful relationships with them and show that you value them, their culture, and their ways of learning, which may be different from traditional ways of learning. This goes beyond merely respecting students and their differences. You build safe spaces for ethnically diverse students to learn and achieve. You provide high expectations for all learners, yet help them succeed in steps, not all at once.
• You respond to ethnic diversity while delivering instruction. You actively seek out ways to incorporate your students’ lives and cultures into the science lessons you’re providing.

Now why is this all so important? For one, research shows that academic scores increase when you deliver culturally relevant instruction (Au & Kawakami, 1994; Boykin & Noguera, 2011; Foster, 1995; Gay, 2000, 2010; Hollins, 1996; Ladson-Billings, 1994, 1995; Paris, 2012; Scherff & Spector, 2011). Boutte, Kelly-Jackson, & Johnson (2010) emphasize that: “academic achievement is a central goal of culturally relevant teaching.” When you set high expectations for students, which for starters can be as simple as calling them “scientists” no matter their age, it shows that you believe they can achieve great things. They feel valued. Secondly, many minority students have spent their entire lives having to fit into a dominant culture, while their own culture has been suppressed, oppressed, and devalued. This has a profound affect on an individual’s identity. It forces one to try and maintain one identity at home and in their community, and a separate identity at school. Imagine what that feels like.

Teaching from a culturally relevant framework supports and nurtures student identities and values. It creates a safe space that allows students to excel, and sometimes to fail. But when failing in a supportive environment, you can help them get back up and try again, step by step. It is this scaffolding of learning that helps struggling performers engage with learning and to advance.

So how do you apply culturally relevant teaching to science? For starters, be willing to look at your own beliefs and biases toward others. Take a few implicit bias tests (https://implicit.harvard.edu/implicit/takeatest.html). Understand that we all have unconscious biases. While difficult, seek out ways to challenge your assumptions (https://www.psychologytoday.com/blog/sound-science-sound-policy/201501/overcoming-implicit-bias-and-racial-anxiety). Learn about and interact with other cultures. Put yourself in others’ shoes. Be the curious scientist you know yourself to be. In the process, you might even find ways to mitigate the global stereotype that all scientists are White males that wear glasses and like to blow things up in the laboratory (Finson, 2002).

Next, get to know the population you serve even more. You could start by administering a student inventory (http://www.cultofpedagogy.com/products-for-your-classroom/). Or have the classroom teacher administer a survey. What you learn can help you to build an authentic relationship and can generate ideas for ways to incorporate a student’s culture into your lessons. Don’t make assumptions about who they are. Find out who they are.

Deal directly with controversial subjects such as racism, sexism, homophobia, and poverty. Give them context. You might think about how science has historically been done by and for men, and how this has shaped the field (e.g., medical dosages are prescribed similarly for men and women, yet women sometimes need a lower dose). How might a discussion about this change the way we do/view science? What can you and your students do about it? While genetics education might start with Gregor Mendel, communities like the Native Americans have been doing experiments on corn for thousands of years but didn’t write down their findings because they followed an oral tradition. How might a Native student who brings this prior knowledge into the classroom then respond to a teacher who posits Mendel as the founder of genetics?

Study a wide range of individuals and ethnic groups. Include many perspectives. No one person represents a group. Again, this is true for you as well as each student in your class. What interests you? Where is there commonality with your students?

How might you infuse issues of social justice, for example, into a science activity? One example involves teaching students science vocabulary (http://www.cultofpedagogy.com/culturally-responsive-teaching-strategies/). Author Zanetta Hammond suggests making a game of it, making the activity a social one, or “storifying” it. All three strategies employ the techniques of oral traditions—listening, repetition, memorization and learning—which are common to many cultures. In addition, marginalized populations often share a history of having to pool their resources in order to survive or get ahead, and value their community and group over individual gain. Creating groups where students can socialize and work together is not only inclusive of all cultures, but models the collaborative nature of scientific work.

Help students make connections between the science content, the contributions made by underrepresented scientists, and your students’ lives. This does not mean you change the science content. But you can incorporate data, photos, examples, and information from different cultures into each lesson so multicultural science education is institutionalized in your program and practices, as opposed to being taught in isolation (e.g., during Women’s History Month only). If you are working with African-American learners, you could talk about and show photos of prominent African-American scientists (e.g., biologists Ernest Just and Charles Drew), show data and graphs of diseases that disproportionately affect African Americans, or provide examples of scientific research that has been done to African Americans (e.g., Tuskegee experiment). By utilizing the techniques of science—such as the scientific method, arguing from evidence, and problem solving—you can elucidate and challenge stereotypes and prejudices.

You might frame a genetics unit not around Gregor Mendel, but around researchers of color: Priya Moorjani, a geneticist who has used genomic data to understand the origins of the Indian caste system; Kono Yasui, a biologist who researched the genetics of several plant species; or Rick Kittles who used genetics to trace the ancestry of African Americans. Or you might choose a woman like Barbara McClintock who was not encouraged personally or professionally to study science, but who still went on to win the Nobel Prize for her work in genetics. Here we have several examples that are inclusive of women’s contributions to science (also see http://news.nationalgeographic.com/news/2013/13/130519-women-scientists-overlooked-dna-history-science/). Pay attention to areas of intersectionality. Are there LGBT researchers you know of? Look for these role models, many of which may be “hidden” or ignored, and celebrate them. The key is that you are not teaching specifically to a particular ethnicity or group, but are incorporating different perspectives and creating an inclusive, relevant, and supportive environment for learners from various backgrounds.

While some of these ideas may give you pause —perhaps you feel they require too much effort or take you too far outside your comfort zone—you don’t have to include everything, or even everything all at once (1). Start with small changes, and identify where you and your students share common ground and what you are comfortable with. Feel free to share activities and examples you find in the comments below. Challenge yourself over time to go beyond a casual interpretation of culture in your science classes and in your lab but instead think about how your lessons might allow for opportunities for critical debates on the role and practices of science in society (Ladson-Billings, 2014). I argue that by not expanding upon our current view of science knowledge and oppression’s role in shaping it, we reinforce and privilege Eurocentric hegemonic ideas. By teaching to the whole child, you will gift your students with strong identities, new perspectives, and ultimately will engage them more in science, increase their critical thinking skills, spur greater learning gains, and hopefully help them consider a career in the sciences. And who doesn’t want that?

(1) For a good philosophical framework, see the “typology for multiculturalizing science” at Baptiste, H., & Key, S. (1996). Cultural Inclusion: Where does your program stand? The Science Teacher, 63(2), 32-35. Retrieved from http://www.jstor.org/stable/24149767

References

Au K.H., & Kawakami, A.J. (1994). Cultural congruence in instruction. In E.R. Hollins, J.E. King, & W.C. Hayman (Eds.), Teaching diverse populations: Formulating a knowledge base (pp. 5–23). Albany: State University of New York Press.

Boutte, G., Kelly-Jackson, C., & Johnson, G.L. (2010). Culturally relevant teaching in science classrooms: Addressing academic achievement, cultural competence, and critical consciousness. International Journal of Multicultural Education, 12(2).

Boykin, A.W., & Noguera, P. (2011). Creating the Opportunity to Learn: Moving from Research to Practice to Close the Achievement Gap. Alexandria, VA: the Association for Supervision and Curriculum Development (ASCD). http://www.ascd.org/publications/books/107016.aspx

Finson, K.D. (2002), Drawing a Scientist: What We Do and Do Not Know After Fifty Years of Drawings. School Science and Mathematics, 102: 335–345. doi:10.1111/j.1949-8594.2002.tb18217.x

Foster, M. (1995). African American teachers and culturally relevant pedagogy. In J.A. Banks & C.A.M. Banks (eds.), Handbook of research on multicultural education (pp. 570–581). New York: Macmillan.

Gay, G. (2000). Culturally responsive teaching: Theory, research, and practice. New York: Teachers College Press.

Gay, G. (2010). Culturally responsive teaching, 2nd Ed. New York, New York: Teachers College Press.

Hollins, E.R. (1996). Culture in school learning: Revealing the deep meaning. Mahwah, NJ: Lawrence Erlbaum.

Ladson-Billings, G. (1994). The Dreamkeepers: Successful teaching for African-American students. San Francisco: Jossey-Bass, pp. 17–18.

Ladson-Billings, G. (1995). Toward a theory of culturally relevant pedagogy. American Educational Research Journal, 32(3), 465–491.

Ladson-Billings, G. (2014). Culturally relevant pedagogy 2.0: aka the remix. Harvard Educational Review, 84(1), 74-84.

Paris, D. (2012). Culturally sustaining pedagogy: A needed change in stance, terminology, and practice. Educational Researcher, 41(3), 93-97.

Scherff, L., & Spector, K. (2011). Culturally relevant pedagogy: Clashes and confrontations. Lanham: Rowman & Littlefield Education.

Shuda, J.R., Butler, V.G., Vary, R., & Farber, S.A. (2016) Project BioEYES: Accessible Student-Driven Science for K–12 Students and Teachers. PLoS Biol 14(11): e2000520. doi:10.1371/journal.pbio.2000520

(7 votes)

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Here are the highlights from the current issue of Development:

ECM: bridging the gap between germ layers

The extracellular matrix (ECM) plays crucial roles during morphogenesis but how it is assembled and patterned in vivo is poorly understood. Here, Yuki Sato, Rusty Lansford and colleagues investigate this by examining the distribution of the ECM component fibronectin (FN) in quail embryos (p. 281). They reveal that FN fibrils form pillars that span the gap between somites and the endoderm. The tissue-specific depletion of FN reveals that both the somites and endoderm provide FN that contributes to these pillars. The authors also observe filopodia-like structures that extend from the basal surface of somatic epithelial cells and are oriented along FN pillars. The formation of these filopodia influences the formation of FN pillars, while the polymerisation of FN is shown to modulate both pillar formation and filopodial elongation. Importantly, both structures are required for proper somite morphogenesis. Finally, the researchers report that blood flow in the nascent dorsal aorta (DA), which is located between the somites and endoderm, controls FN pillar distribution; disruption of DA formation, or occlusion of the DA, leads to a scattered distribution of FN pillars. Together, these findings suggest that pulsations from the DA help establish FN pillars that bridge the somite-endoderm gap and potentially aid communication between these tissues.

Brainy roles for cilia and mTORC1

During vertebrate brain development, neurons and glia arise from a population of self-renewing radial glial cells (RGCs) that contact the cerebral ventricles and bear a primary cilium. Primary cilia are known to play crucial roles in signalling but it is not clear if they are required for morphogenesis. Now, on p. 201, Nathalie Spassky and co-workers show that primary cilia on RGCs are essential for proper ventricular morphogenesis in mice. They first report that ciliary mutant mice exhibit enlarged lateral ventricles (ventriculomegaly) and reduced cortical thickness. The absence of primary cilia also leads to an increase in the size of RGC apical domains. This apical endfoot enlargement, the authors report, is associated with spindle orientation defects and is caused by upregulation of the mTORC1 pathway. Accordingly, treatment with rapamycin – an mTORC1 inhibitor – prevents apical domain enlargement in ciliary mutants and rescues their ventriculomegaly phenotype. Overall, this study reveals a new role for the mTORC1 pathway in regulating ventricle morphogenesis and corticogenesis, suggesting that it constitutes a new potential therapeutic target for the treatment of ventriculomegaly.

Getting to the root of brassinosteroid function

The plant hormone brassinosteroid (BR), which signals through its receptors BR INSENSITIVE 1 (BRI1), BRI1-LIKE 1 (BRL1) and BRL3, is known to regulate hypocotyl elongation but how it functions in the root is less clear. In this issue, Christian Hardtke and colleagues assess the role of BR during cell differentiation in the Arabidopsis root (p. 272). They first show that bri1 brl1 brl3 triple mutants display protophloem differentiation defects. These defects cannot be rescued by activating BR signalling in adjacent cell files, suggesting that BR acts in a cell-autonomous manner to control protophloem differentiation. Triple mutants also exhibit a small meristem, and the authors show that this can be explained by reduced cell elongation that, together with increased formative divisions in the radial dimension, contributes to the overall reduction in root growth observed in these mutants. Finally, the researchers demonstrate that the protophloem-specific activation of BR signalling can rescue all major aspects of the triple mutant phenotype, thus uncovering a new facet of the non-cell-autonomous effects of BR signalling. Based on these and other findings, the authors propose that BR perception in the protophloem is sufficient to systemically convey BR action within the root meristem.

PLUS…

Primate embryogenesis predicts the hallmarks of human naïve pluripotency

Naïve pluripotent mouse embryonic stem cells (ESCs) resemble the preimplantation epiblast and efficiently contribute to chimaeras. By contrast, primate ESCs correspond to the postimplantation embryo and fail to resume development in chimaeric assays. In their Hypothesis article, Thorsten Boroviak and Jennifer Nichols  discuss these differences, highlighting several fundamental differences between rodent and primate early development, and exploit them to predict key hallmarks of naïve pluripotency in primates.

Planar cell polarity in moving cells: think globally, act locally

The planar cell polarity (PCP) pathway is best known for its role in polarizing epithelial cells within the plane of a tissue but it also plays a role in a range of cell migration events during development. In their Review, Crystal Davey and Cecilia Moens highlight recent discoveries regarding the localization of PCP proteins in migrating cells and their impact on the cell biology of collective and individual cell migratory behaviors.

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Comment on “Neuronal sources of hedgehog modulate neurogenesis in the adult planarian brain”, eLife 2016;5:e19735.

Currie et al., eLife (2016)

Ko W. Currie, Cellular Neurobiology, Institut de recherches cliniques de Montreal (IRCM), Montreal, QC

Alyssa M. Molinaro, Hospital for Sick Children, Toronto, ON

Bret J. Pearson, Hospital for Sick Children, Toronto, ON

To say that biologists have been studying freshwater planarians for a long time is a huge understatement, with one of the earliest known description of planarian regeneration dating back to 1766 (Pallas 1766). Many early naturalists and embryologists marvelled at the planarian’s ability to completely regenerate from any injury, even re-constructing an entirely new body plan from tiny tissue fragments. Even the famed Drosophila geneticist Thomas Hunt Morgan, enjoyed a brief stint experimenting with these flatworms, before moving on to the problem of genetic inheritance (Morgan 1898). Despite this earlier interest, planarians largely fell out of fashion as a model system for developmental biology for roughly an entire century.

I joined Bret’s lab in the Fall of 2010, at a time when planarian research had just enjoyed a dramatic 10-year resurgence. We were now able to specifically visualize the planarian stem cells (also known as “neoblasts”) that granted these flatworms their regenerative powers, and had uncovered some of the genes that regulated their proliferation and differentiation into the various somatic cells of the mature organ systems (Reddien et al., 2005). The genome of the most commonly used lab species, Schmidtea mediterranea, had recently been sequenced (Robb et al., 2008), and many of the fundamental cell signaling pathways, including the Hedgehog pathway, had been assessed for functions during large-scale regeneration events (Gurley et al., 2008; Reddien et al., 2007; Rink et al., 2009). However, significantly less attention had been focused on the planarian nervous system, which must be precisely re-constructed following decapitation, so that the new organ grows to the correct size in proportion with the rest of the body and that all of the mature neurons are regenerated in the proper cellular ratios, thereby bringing about full recovery of brain function.

Earlier studies demonstrated the surprising molecular complexity of the planarian nervous system, but the specific genes and signaling mechanisms that regulated its construction were still largely unknown. Therefore, we set our sights on some very basic questions; 1) Within the large pool of planarian neoblasts, are there dedicated neural stem cells that are required for brain regeneration? 2) How are specific neural cell types specified/differentiated from upstream stem cells? 3) What extrinsic cell signals control the rate of neurogenesis during regeneration and in homeostatic (uninjured) conditions?

With these broad goals in mind, we did what most people do when you don’t have a concrete starting point, we did a screen. Taking advantage of the fact that planarians are susceptible to RNAi gene knockdown through feeding (a mixture of beef liver paste and E. coli that are forced to express double-stranded RNA for your gene of interest), it was possible to perform a high-throughput RNAi screen. We identified over one hundred planarian homologs of well-established neuronal regulatory genes, including many homeobox transcription factors, and proceeded to knock each one down, testing for possible functions in the planarian nervous system.

Since we were knocking down homologs of canonical neural stem cell regulators such as Pax6 and Sox2, we were really hoping that following decapitation, some of these RNAi-treated flatworms would exhibit major defects in brain regeneration. Alas, as is often the case in science, we never got such striking results. However, what we did notice, was that a fair number of RNAi-treated worms (even without decapitation) exhibited an array of strange/aberrant behaviours (including paralysis, and some very odd involuntary muscular contractions), that we thought could be caused by neuronal dysfunction within the intact nervous system. Therefore, we decided to focus on the transcription factors which yielded behavioural defects after RNAi-knockdown, examining them for neuronal specification defects.

Among these genes causing strange animal behaviours were two homologs of homeobox transcription factors, nkx2.1 and arx. In particular, knockdown of nkx2.1, caused a very striking muscular contraction defect seen above (colloquially called the “cobra” phenotype in our lab), resulting in the animals constantly rearing back their heads so that they swam with their head perpendicular with the rest of the body, similar to a cobra snake. When we examined the brains of planarians after RNAi against nkx2.1 and arx, we found that these worms were missing a significant number of neurons belonging to the cholinergic, GABAergic and octopaminergic neural subtypes, specifically in the medial-most region of the brain (see image below), implicating these two transcription factors in the specification of these neuronal populations. Interestingly, we also found planarian stem cells immediately adjacent to this brain region that expressed nkx2.1 and arx, leading us to speculate that within this microenvironment (see image below), there may be communication between the mature neurons and their upstream stem cells to regulate their own production.

To investigate what this signal might be, we decided to look at the Hedgehog signaling pathway. It was already known that the planarian hedgehog (hh) ligand was expressed in the medial regions of the CNS (Rink et al., 2009). But we showed more specifically that the hh signaling molecule was actually expressed in the very same medially-located neuron subtypes as nkx2.1 and arx. In addition, we found that stem cells located right next to the brain expressed the Hedgehog receptor patched, as well as the downstream effector genes, smoothened and gli-1, demonstrating that planarian stem cells were likely capable of receiving and responding to hh signals coming from the mature brain.

Next, we had to actually test whether hh signaling had any functional consequence on neurogenesis levels. For all of the interesting biology and techniques that are now available within the planarian research community, we still don’t have true genetic tools such as transgenics to perform gene knockout or overexpression experiments in a targeted cell-specific manner. Instead, we had to rely on organism-wide gene knockdown experiments to globally decrease or increase hh signaling, which admittedly I was a little nervous about, due to the wide range of roles that the hh pathway plays in animal development. Luckily, we found that when we knocked down the planarian hh ligand (decreased signaling activity), this resulted in the production of fewer neural progenitor cells as well as new mature cholinergic neurons, while having little to no effect on other tissue lineages (skin, gut & pharynx).

We were initially a little confused by the result, since one would expect that in an intact “steady-state” brain, any signals coming from these mature neurons would actively repress the production of new neurons, whereas brain injury or the removal of nervous tissue would promote stem cells to increase their neuronal output. Instead, our results indicate the opposite, where hh signals coming from medial neurons are actually required to promote adult neurogenesis. It is possible that hh acts to counter and balance out the effects of local Wnt signaling, which has been shown to repress brain expansion by limiting neuronal progenitor production (Hill & Petersen 2015). However, it should also be noted that in the mammalian CNS, Sonic Hedgehog has known mitogenic roles, where its local production by differentiating or mature neurons signals back onto neural progenitors and adult neural stem cells to promote cell proliferation levels (Alvarez-Buylla & Ihrie 2014; Ihrie et al., 2011). Interestingly, this wasn’t the only parallel with the mammalian CNS, as Nkx2.1 and Arx are part of a transcription factor cascade within the early ventral telencephalon that specifies GABAergic and cholinergic interneurons (Butt et al., 2008; Vogt et al., 2014). I find it extremely interesting that across this huge evolutionary gap, these same transcription factors and this hedgehog signaling axis between mature neurons and stem cells have retained the same developmental functions in vastly different organisms. It also gives me reassurance about the importance of studying non-traditional model organisms, as the underlying basic biology is often conserved, so our findings from planarians, Hydra, Nematostella, Parhyale and other emerging lab models can be hugely informative for future studies on mammals and even humans.

References

Alvarez-Buylla A & Ihrie RA. (2014). Sonic hedgehog signaling in the postnatal brain. Seminars in Cell & Developmental Biology 33: 105-111. http://www.sciencedirect.com/science/article/pii/S1084952114001451

Butt SJ, Sousa VH, Fuccillo MV, Hjerling-Leffler J, Miyoshi G, Kimura S & Fischell G. (2008). The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes. Neuron 59: 722-732.  http://www.sciencedirect.com/science/article/pii/S0896627308006302

Gurley KA, Rink JC & Sanchez Alvarado A. (2008). β-catenin defines head versus tail identity during planarian regeneration and homeostasis. Science 319: 323–327.  http://science.sciencemag.org/content/319/5861/323

Hill EM & Petersen CP. (2015). Wnt/Notum spatial feedback inhibition controls neoblast differentiation to regulate reversible growth of the planarian brain. Development 142(24): 4217-29. http://dev.biologists.org/content/142/24/4217

Ihrie RA, Shah JK, Harwell CC, Levine JH, Guinto CD, Lezameta M, Kreigstein AR & Alvarez-Buylla A. (2011). Persistent sonic hedgehog signaling in adult brain determines neural stem cell positional identity. Neuron 71: 250-262. http://www.sciencedirect.com/science/article/pii/S0896627311004041

Morgan, T. H. (1898). Experimental studies of the regeneration of Planaria maculata. Arch. Entwm. Org. 7: 364–397. *This paper was subject of one of the Node’s Forgotten Classics posts*

Pallas, P. S. (1766). Miscellanea zoologica, quibus novae imprimis atque obscurae animalium species. Hagae Comitum, apud Pterum van Cleef, Holland.

Reddien PW, Bermange AL, Kicza AM & Sanchez Alvarado A. (2007). BMP signaling regulates the dorsal planarian midline and is needed for asymmetric regeneration. Development 134: 4043–4051. http://dev.biologists.org/content/134/22/4043

Reddien PW, Bermange AL, Murfitt KJ, Jennings JR & Sanchez Alvarado A. (2005). Identification of genes needed for regeneration, stem cell function, and tissue homeostasis by systematic gene perturbation in planaria. Developmental Cell 8: 635–649.  http://www.sciencedirect.com/science/article/pii/S1534580705000924

Rink JC, Gurley KA, Elliott SA & Sanchez Alvarado A. (2009). Planarian Hh signaling regulates regeneration polarity and links Hh pathway evolution to cilia. Science 326: 1406–1410. http://science.sciencemag.org/content/326/5958/1406.long

Robb SM, Ross E & Sanchez Alvarado A. (2008). SmedGD: the Schmidtea mediterranea Genome Database. Nucleic Acids Res 36: D599–D606.

Vogt D, Hunt RF, Mandal S, Sandberg M, Silberberg SN, Nagasawa T, Yang Z, Baraban SC & Rubenstein JL. (2014). Lhx6 directly regulates Arx and Cxcr7 to determine cortical interneuron fate and laminar position. Neuron 82: 350-364.  http://www.cell.com/neuron/abstract/S0896-6273(14)00161-5

(3 votes)

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The New Year’s honours list recognises citizens who have made achievements in public life and committed themselves to serving and helping Britain.

This year three prominent developmental and stem cell biologists were honoured, putting our field in the national news. The Development team were especially happy that two of the newly honoured researchers have connections to the journal: Sir Jim Smith was Development’s Editor in Chief from 2003-2009, and Dame Ottoline Leyser is currently one our editors. Dame Amanda Fisher has also been recognised for her contributions to stem cell and HIV research. The recognition of all three also includes their promotion of women in science.

Ottline Leyser’s bio from the page announcing the awards

Professor (Henrietta Miriam) Ottoline Leyser CBE Professor Leyser, Director of the Sainsbury Laboratory at the University of Cambridge, is an inspirational scientist who has made seminal contributions to plant biology with direct implications for agricultural crops. Among many other awards, she was given the 2016 Genetics Society Medal in recognition of her work which has maintained the UK’s scientific leadership in this field. She was President of International Plant Molecular Biology and is a Foreign Associate of the US National Academy of Sciences. She has been a passionate advocate of career development for young researchers, especially women, and won the Royal Society’s Rosalind Franklin Award in 2007 for her proposal on combining a research career and a family.

Jim Smith’s bio

Dr. Smith, Director of Science at the Wellcome Trust and Senior Group Leader at the Francis Crick Institute, is a scientific leader who has transformed our understanding of embryonic development, giving insights into genetic defects in children and how stem cells develop into different tissues. He played a leading role in the development of the Francis Crick Institute from its early beginnings to its establishment in 2015. Previously, as Director of the Gurdon Institute and then of the MRC National Institute for Medical Research, he provided leadership in UK science across a breadth of disciplines and helped nurture the next generation of outstanding scientists, taking particular care to promote the careers of women.

Amanda Fisher’s bio

Professor Fisher, Director of the MRC Clinical Sciences Centre at Imperial College, London, has made fundamental discoveries in the molecular biology of HIV, the genomic characterisation of stem cells and the study of epigenetic gene regulation. Her observations of the HIV-1 virus underpinned the complete molecular understanding of the HIV genome and were a basis for the subsequent development of antiretroviral drugs. She is a strong advocate and role model for women in science and has made a significant contribution to the public understanding of science and training and mentoring researchers.

Many developmental biologists have also benefited from the technological advances made by another newly recognised Knight, Shankar Balasubramanian

Professor Shankar Balasubramanian Professor Balasubramanian, Herchel Smith Professor of Medicinal Chemistry at Cambridge University, was co-inventor of Next Generation DNA sequencing, the most transformational advance in biology and medicine for decades. Solexa sequencing, as it is now known, allows an individual genome to be sequenced in a day or two at a cost of less than £1000; previously, sequencing the human genome took years of work and cost billions. His work has spawned an entirely new discipline of Bioinformatics. More recently, he has made major contributions to understanding the role of DNA-quadruplexes in cancer and invented a method for the sequencing of epigenetic modifications.

Congratulations to the newly honoured!

(3 votes)

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In September 2016, Development held its second meeting dedicated to human development. You can read about the meeting in a review by April Craft and Matthew Johnson in this week’s issue, and a less formal mini-report on the Node in October.

The Development team also did some filming, asking participants about their views on what made the meeting special, as well as the state of the human development field. You can watch the video, and see a gallery of images from the meeting, below.

The Development team, Seema Grewal (Reviews Editor), Katherine Brown (Executive Editor), Caroline Hendry (Reviews Editor) and Aidan Maartens (Community Manager, the Node)

Nicky Le Blond, The Company of Biologists’ Meeting Organiser

Development posters

Beer and posters

Coffee and posters

Coffee and posters

Coffee and posters

Beer and posters

Beer and posters

Yann Barrandon, Guy Sauvageau and Sally Temple in the panel session on clinical applications

The social event was a trip to the American Optical Museum

Old lenses

Dick, the museum’s curator, shows us around

The American Optical Museum

The American Optical Museum

The American Optical Museum

The American Optical Museum

Coffee and beer in the tavern below the museum

Coffee and beer in the tavern below the museum

Coffee and beer in the tavern below the museum

Coffee and beer in the tavern below the museum

The Development team with editors Austin Smith, Benoit Bruneau and Gordon Keller

Coffee and beer in the tavern below the museum

Coffee and beer in the tavern below the museum

Final night dinner

Final night dinner

Final night dinner

Final night dinner

Table pics by Ray Dunn

Table pics by Ray Dunn

Table pics by Ray Dunn

Table pics by Ray Dunn

Table pics by Ray Dunn

Table pics by Ray Dunn

Table pics by Ray Dunn

Table pics by Ray Dunn

Table pics by Ray Dunn

Table pics by Ray Dunn

(1 votes)

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Department/Location: Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute

Salary: £34,956-£46,924

Reference: PS11107

Closing date: 08 February 2017

Applications are invited for the position of Principal Technician to the Wellcome-MRC Cambridge Stem Cell Institute. The post holder will work closely with the Department of Haematology as both prepare to move together into a new purpose-built building (Capella) on the Cambridge Biomedical Campus. The Cambridge Stem Cell Institute and Department of Haematology are both led by Professor Tony Green. This is an exciting time and the post holder will help shape the transition to our new building.

The Cambridge Stem Cell Institute is a world-leading centre of excellence in stem cell biology and regenerative medicine, supported by the Wellcome Trust and the Medical Research Council (www.stemcells.cam.ac.uk). The Institute will comprise ~32 group leaders, ~28 affiliated group leaders, over 350 scientists, occupying 10,000 sqm and with an active grant portfolio of ~100 million.

Until 2018 the post holder will be based in the Gleeson building and will oversee building, facilities and laboratory support for CSCI groups in that building. The post-holder will have an exciting key role in planning the CSCI/ Haematology laboratory-focussed support structures needed in Capella, will plan and coordinate the move of all CSCI/ Haematology groups and facilities and will work closely with the Capella Technical Liaison Officer. Once in Capella the post holder will be responsible for establishing and managing the laboratory focussed operational structures for CSCI/ Haematology to achieve scientific and strategic objectives. In particular the individual will ensure the smooth and efficient day-to-day running of ~32 laboratories and associated specialist facilities and will work closely with the Capella buildings and services team.

Applicants should have a degree in Biological science or related subject as well as excellent motivational and interpersonal skills. Extensive experience of laboratory management is essential as is previous experience of hands-on research. Experience in managing building projects and refurbishments, building services and health and safety would all be desirable. You should be able to demonstrate experience in supervision and performance management and will have excellent written and oral communication skills. You will be responsible for procurement and purchasing of high value goods and services and must have a good understanding of financial accounting processes. Familiarity with University Financial System is desirable but training can be provided. Once in the new building it is likely that the duties of this post will evolve so adaptability and flexibility are essential.

Once an offer of employment has been accepted, the successful candidate will be required to undergo a security check.

Limited funding: The funds for this post are available until 30 June 2022 in the first instance.

To apply online for this vacancy and to view further information about the role, please visit: http://www.jobs.cam.ac.uk/job/12539. This will take you to the role on the University’s Job Opportunities pages. There you will need to click on the ‘Apply online’ button and register an account with the University’s Web Recruitment System (if you have not already) and log in before completing the online application form.

The closing date for all applications is Wednesday 08 February 2017.

Interviews will be held in mid February.

Informal enquiries are also welcome via e-mail to Louise Balshaw, CSCI Administrator at lb358@cam.ac.uk.

Please quote reference PS11107 on your application and in any correspondence about this vacancy.

The University values diversity and is committed to equality of opportunity.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

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This is the latest dispatch from a recipient of a Company of Biologists Travelling Fellowship.

Learn more about the scheme, including how to apply, here, and read more stories from the Fellows here.

Nanami Morooka

It was spring in 2015 when I first met Dr. Stefan Schulte-Merker in Osaka, Japan. There, it became apparent that both of our laboratories had been interested in same gene and analyzed mutant mice and fish, which develop lymphedema as a consequence of lymphatic defects. Our group have long been interested in extra cellular matrix (ECM) biochemistry. We recently tried to screen functionally unknown ECM proteins and investigated their function using mutant mice. On the other hand, Stefan’s group has studied lymphatic vascular development, and screened novel lymphangiogenic factor using fish. We both took totally different approach at first, but finally reached same gene. In the meeting, we exchanged data and had a great discussion. However, the time was so limited that we could not have enough time for discussion. From then, I hoped to collaborate with Stefan, and fortunately I got a chance to visit to Stefan’s lab by successfully applying for a Company of Biologists Travelling Fellowship.

In 2016 April, I went to Münster in Germany. Münster is a beautiful city that has a lot of historical place and nature side by side. If you walk a little from city center, you can go to a lake Aasee and enjoy winds of nature. Every Wednesday and Saturday, an open-air market is held in front of Dome, and it soon became my favorite thing. Everyday, after having delicious bread and cheese for breakfast, I went to Stefan’s lab.

The main purpose of my stay was learning how to observe whole mouse embryo staining using ultramicroscopy technique (thanks to cooperation with Dr. Kiefer ). I also learned zebrafish experiments so I could learn merits using fish. During these experiments, I could share detailed practical information, which I could not get from research articles. Furthermore, we had several meetings. It was really important for me, because I could share ideas with vascular biologists. They provided me a lot of advice that I never thought about it. At the same time, I could return my opinions as an ECM biologist, which brings me to realize what is my strength point and what I have to study more. Now I think I can understand my research better than before.

“During these experiments, I could share detailed practical information, which I could not get from research articles. Furthermore, we had several meetings. It was really important for me, because I could share ideas”

I would like to thank Stefan and lab members for their hospitality. They always talked to me friendly and asked me to lunch. Many of them gave their time for me to teach experiments and to have meetings. Stefan kindly showed me around town. He took me to café several times so that we could talk not only about science itself but also about scientific things, like career or the system of scientific research in Germany. It helps me to think about my future as a scientist. After visiting to Stefan’s lab, I re-boost up my motivation in research, and I came up with new ideas. This collaboration was really profitable. I do not doubt that it will improve lymphatic vascular research.

(2 votes)

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• Researchers at IRB Barcelona identify a fundamental role of the JAK/STAT signalling pathway in the development and growth regulation of limbs in Drosophila.
• Published in Nature Communications, the study paves the way to research into the function of this pathway in vertebrate development and its possible involvement in human congenital diseases.

Many of the secrets of life, such as how we become a certain size and shape, have been uncovered in studies performed over more than 100 years and involving animal models such as the fruit fly Drosophila melanogaster. Now, IRB Barcelona researchers headed by ICREA Professor Marco Milán disclose a new signal that participates in the specification and growth of fly wings.

In Nature Communications, the scientists conclude that the JAK/STAT signalling pathway, known to be tightly linked to inflammatory processes and tumour growth, determines where, when and how a wing develops in Drosophila. PhD student Carles Recasens, who will defend his thesis with the results of this study in January, has discovered that “JAK/STAT appears at key time points in the development of the appendage and that it collaborates with Wingless/Wnt, Dpp/BMP and Hedgehog in wing specification and growth”. These findings pave the way to studying the participation of JAK/STAT in human development and its possible implications in congenital diseases that involve limb malformation.

“Given the similarities in the molecules and the mechanisms involved in limb development in vertebrates and invertebrates, the fly is a very useful genetic model in which to identify new genes that potentially participate in limb development in vertebrates and their possible association with congenital diseases,” says Ana Ferreira, who has participated in the study. Marco Milán, head of the Development and Growth Control Lab, adds that “the patterns that determine how flies and humans are built are very similar and the basic molecular mechanisms have been conserved throughout evolution. We share a lot of basic biology and we increasingly find that what happens in flies also happens in humans”.

This work has identified three defined functions of JAK/STAT in fly development. First, it cooperates with Wingless (Wnt in humans) to specify where the wing will develop. Second, it helps cells that produce Hedgehog (Sonic hedgehog in humans) to survive and proliferate in order to induce the expression of Dpp (BMP in humans), a molecule that organises the patterning and growth of the whole wing. And third, it delimits the action of Dpp so that the wing grows in the right place. In summary, JAK/STAT controls the three main cell signals responsible for the specification and growth of limbs, both in vertebrates and invertebrates.

Carles Recasens and Ana Ferreira will be joining the recently opened Francis Crick Institute in London to undertake postdoc training, during which they will continue to address the fruit fly.

Reference article:

JAK/STAT controls organ size and fate specification by regulating morphogen production and signalling

Carles Recasens-Alvarez, Ana Ferreira and Marco Milán

Nature Communications (2017): http://www.nature.com/articles/ncomms13815

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Our latest monthly trawl for developmental biology (and other cool) preprints. See June’s introductory post for background, and let us know if we missed anything

2016 saw preprints in the life sciences really taking off…

bioRxiv ends the year on a high pic.twitter.com/D8nm136oYF

— Richard Sever (@cshperspectives) January 3, 2017

…and, perhaps in light of Jim Woodgett’s advice…

If you’re about to submit a manuscript:
1 Stop 🚫
2 Deposit @biorxivpreprint
3 Chill
4 Enjoy Holidays 🥂🎉🎊
5 Submit to journal in January ❤️

— Jim Woodgett (@jwoodgett) December 14, 2016

…lots of preprints were deposited in December, predominantly on bioRxiv, though we also found a handful on arXiv, PeerJ, and our first entry from the recently launched Wellcome Open Research.

Three papers from the Martin-Blanco lab investigated various aspects of signalling and morphogenesis in flies, fish and brachiopods with some beautiful live imaging. There was more embryo mechanics, this time using c. elegans, from Michel Labouesse’s group, some Hox regulatory dynamics from Robb Krumlauf’s group, and two preprints on the stem cell ground state from Austin Smith’s group. Plus some plants (including tree development from Torgeir Hvidsten’s lab and work on auxin by the newly honoured Dame Ottoline Lesyer and colleagues), the problems with null hypothesis significance testing, and a whole bunch of tools and resources. Happy preprinting!

Developmental biology

Morphogenesis & Differentiation

The Dachsous/Fat/Four-jointed pathway implements axial long-range cell orientation. Federica Mangione, Enrique Martin-Blanco

The architectural balance of the Ventral Nerve Cord depends on the level of JNK signaling activity. Katerina Karkali, George Panayotou, Timothy E Saunders, Enrique Martin-Blanco

Rab5-mediated Yolk Endocytosis modulates Zebrafish Epiboly Biomechanics and Tissue Movements. Maria Marsal, Amayra Hernandez-Vega, Philippe-Alexandre Pouille, Enrique Martin-Blanco

The interplay of stiffness and force anisotropies drive embryo elongation. Thanh Thi Kim Vuong-Brender, Martine Ben Amar, Julien Pontabry, Michel Labouesse

Fractone bulbs derive from ependymal cells and their laminin composition affects cell proliferation in the subventricular zone. Marcos Assis Nascimento, Tatiana Coelho-Sampaio, Lydia Sorokin

Early survival and delayed death of developmentally-born dentate gyrus neurons. Shaina P Cahill, Ru Qi Yu, Dylan C Green, Evgenia V Todorova, Jason Scott Snyder

Ras/ERK-signalling promotes tRNA synthesis and growth via the RNA polymerase III repressor Maf1 in Drosophila. Shrivani Sriskanthadevan-Pirahas, Rujuta Deshpande, Byoungchun Lee, Savraj Grewal

Blood flow directs arterial-venous remodeling through Notch activation and endothelial cell migration. Bart Weijts, Edgar Gutierrez, Semion K Saikin, Ararat J Ablooglu, David Traver, Alex Groisman, Eugene Tkachenko

Zebrafish Nanog is not required in embryonic cells. James A Gagnon, Kamal Obbad, Alexander F Schier

Ca2+ dynamics in zebrafish hyper-dorsalization of congenital anomaly. Yusuke Tsuruwaka, Eriko Shimada.

Genes and transcription

Hoxa1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on Hoxa1 targets. Bony De Kumar, Hugo J Parker, Ariel Paulson, Mark E Parrish, Irina Pushel, Brian D Slaughter, Jay R Unruh, Julia B Zeitlinger, Robb Krumlauf

The Aquarius/EMB-4 helicase licenses co-transcriptional gene silencing. Alper Akay, Tomas Di Domenico, Kin Man Suen, Amena Nabih, Guillermo Eduardo Parada, Mark Larance, Ragini Medhi, Ahmet Can Berkyurek, Christopher J. Wedeles, Xinlian Zhang, Ping Ma, Angus I. Lamond, Martin Hemberg, Julie M. Claycomb, Eric Alexander Miska

Optimal decoding of information from a genetic network. Mariela D. Petkova, Gašper Tkačik, William Bialek, Eric F. Wieschaus, Thomas Gregor.

TAF10 is required for the integrity of TFIID and SAGA complexes but is initially dispensable for somitogenesis in the mouse embryo. Paul Bardot, Stephane D Vincent, Marjorie Fournier, Alexis Hubaud, Mathilde Joint, Laszlo Tora, Olivier Pourquie

Human pancreatic β cell lncRNAs control cell-specific regulatory networks. Ildem Akerman, Zhidong Tu, Anthony Beucher, Delphine Rolando, Claire Sauty-Colace, Marion Benazra, Nikolina Nakic, Jialiang Yang, Huan Wang, Lorenzo Pasquali, Ignasi Moran, Javier Garcia-Hurtado, Natalia Castro, Roser Gonzalez-Franco, Andrew F. Stewart, Caroline Bonner, Lorenzo Piemonti, Thierry Berney, Leif Groop, Julie Kerr-Conte, Francois Pattou, Carmen Argmann, Eric Schadt, Philippe Ravassard, Jorge Ferrer

Stem cells

Tracking the embryonic stem cell transition from ground state pluripotency. Tuzer Kalkan, Nelly Olova, Mila Roode, Carla Mulas, Heather J Lee, Isabelle Nett, Hendrik Marks, Rachael Walker, Hendrik G Stunnenberg, Kathryn Lilley, Jennifer Nichols, Wolf Reik, Paul Bertone, Austin Smith

Nodal secures pluripotency upon embryonic stem cell progression from the ground state. Carla Mulas, Tüzer Kalkan, Austin Smith

Impact of regulatory variation across human iPSCs and differentiated cells. Nicholas E Banovich, Yang I Li, Anil Raj, Michelle C Ward, Peyton Greenside, Diego Calderon, Po Yuan Tung, Jonathan E Burnett, Marsha Myrthil, Samantha M Thomas, Courtney K Burrows, Irene Gallego Romero, Bryan J Pavlovic, Anshul Kundaje, Jonathan K Pritchard, Yoav Gilad

Quantitative Analysis of Dopamine Neuron Subtypes Generated from Mouse Embryonic Stem Cells. Yu-Ting L. Dingle, Katherine Xiong, Jason T. Machan, Kimberly A. Seymour, Debra Ellisor, Diane Hoffman-Kim, Mark Zervas

DNA damage response decreases during induced pluripotent and embryonic stem cell differentiation. Kalpana Mujoo, Raj K Pandita, Anjina Tiwari, Vijay Charaka, Sharmistha Chakraborti, Walter Hittelman, Nobuo Horikoshi, Clayton Hunt, KumKum Khanna, Alexander Kots, Brian Butler, Ferid Murad, Tej K Pandita

Myotome adaptability confers developmental robustness to somitic myogenesis in response to fibre number alteration. Shukolpa Dutta duttaroy, Victoria C Williams-Ward, Tapan G Pipalia, Chrissy L Hammond, Stefanie Knappe, Robert D Knight, Simon M Hughes, Kuoyu Li

Cadm1 regulates airway stem cell growth and differentiation via modulation of Stat3 activity. Pooja Seedhar, Elizabeth Sage, Sabari Vallath, Gabrielle Sturges, Adam Giangreco

Opportune cell culture conditions permit transfer of the neurosphere paradigm to cells of the cerebellar granule cell lineage by being permissive to sonic hedgehog signaling. Constantin Heil

Plant development

Cross-species functional diversity within the PIN auxin efflux protein family. Devin Lee O’Connor, Mon Mandy Hsia, John Vogel, Ottoline Leyser

High-spatial-resolution transcriptome profiling reveals uncharacterized regulatory complexity underlying cambial growth and wood formation in Populus tremula. David Sundell, Nathaniel R Street, Manoj Kumar, Ewa J Mellerowicz, Melis Kucukoglu, Christoffer Johnsson, Vikash Kumar, Chanaka Mannapperuma, Ove Nilsson, Hannele Tuominen, Edouard Pesquet, Urs Fischer, Totte Niittyla, Bjoern Sundberg, Torgeir R Hvidsten

Malate-dependent Fe accumulation is a critical checkpoint in the root developmental response to low phosphate. Javier Mora-Macias, Jonathan Odilon Ojeda-Rivera, Dolores Gutierrez-Alanis, Lenin Yong-Villalobos, Araceli Oropeza-Aburto, Javier Raya-Gonzalez, Gabriel Jimenez-Dominguez, Gabriela Chavez-Calvillo, View ORCID ProfileRuben Rellan-Alvarez, Luis Rafael Herrera-Estrella

Arabidopsis HAP2/GCS1 is a gamete fusion protein homologous to somatic and viral fusogens. Clari Valansi, David Moi, Evgenia Leikina, Elena Matveev, Martin Grana, Leonid V Chernomordik, Hector Romero, Pablo S Aguilar, Benjamin Podbilewicz

Cell biology

Cell cycle dynamics of chromosomal organisation at single-cell resolution. Takashi Nagano, Yaniv Lubling, Csilla Varnai, Carmel Dudley, Wing Leung, Yael Baran, Netta Mandelson Cohen, Steven Wingett, Peter Fraser, Amos Tanay

Cohesin dependent compaction of mitotic chromosomes. Stephanie A Schalbetter, Anton Goloborodko, Geoffrey Fudenberg, Jon M Belton, Catrina Miles, Miao Yu, Job Dekker, Leonid Mirny, Jon Baxter

A SUMO-Ubiquitin Relay Recruits Proteasomes to Chromosome Axes to Regulate Meiotic Recombination. H.B.D. Prasada Rao, Huanyu Qiao, Shubhang K. Bhatt, Logan R.J. Bailey, Hung D. Tran, Sarah L. Bourne, Wendy Qiu, Anusha Deshpande, Ajay N. Sharma, Connor J. Beebout, Roberto J. Pezza, Neil Hunter

Choreography of budding yeast chromosomes during the cell cycle. Luciana Lazar-Stefanita, Vittore Scolari, Guillaume Mercy, Agnes Thierry, Heloise Muller, Julien Mozziconacci, Romain Koszul

Mechanism of Nuclear Movements in a Multinucleated Cell. Romain Gibeaux, Antonio Politi, Peter Philippsen, Francois Nedelec

The centrosome is a selective phase that nucleates microtubules by concentrating tubulin. Jeffrey B Woodruff, Beatriz Ferreira Gomes, Per O Widlund, Julia Mahamid, Anthony A Hyman

Reversible metamorphosis in a bacterium. Karina Ramijan, Joost Willemse, Eveline Ultee, Joeri Wondergem, Anne van der Meij, Ariane Briegel, Doris Heinrich, Gilles van Wezel, Dennis Claessen

A systematic cell size screen uncovers coupling of growth to division by the p38/HOG network in Candida albicans. Adnane Sellam, Julien Chaillot, Jaideep Mallick, Faiza Tebbji, Julien Richard Albert, Michael A Cook, Mike Tyers

Evolution

Senescence gives insights into the morphogenetic evolution of anamniotes. Eric Villiard, Jean-Francois Denis, Faranak Sadat Hashemi, Sebastian Igelmann, Gerardo Ferbeyre, Stephane Roy

Repeated losses of PRDM9-directed recombination despite the conservation of PRDM9 across vertebrates. Zachary Baker, Molly Schumer, Yuki Haba, Chris Holland, Gil G Rosenthal, Molly Przeworski

Genome sequence of a diabetes-prone desert rodent reveals a mutation hotspot around the ParaHox gene cluster. Adam D Hargreaves, Long Zhou, Josef Christensen, Ferdinand Marletaz, Shiping Liu, Fang Li, Peter Gildsig Jansen, Enrico Spiga, Matilde Thye Hansen, Signe Vendelbo Horn Pedersen, Shameek Biswas, Kyle Serikawa, Brian A Fox, William R Taylor, John F Mulley, Guojie Zhang, R Scott Heller, Peter W H Holland

Two loci contribute epistastically to heterospecific pollen rejection, a postmating isolating barrier between species. Jennafer Hamlin, Natasha Sherman, Leonie C Moyle

Generation of heritable germline mutations in the jewel wasp Nasonia vitri pennis using CRISPR/Cas9. Ming Li, Lauren Yun Cook, Deema Douglah, Abigail Chong, Bradley J White, Patrick Ferree, Omar S Akbari

Parallel adaptation to higher temperatures in divergent clades of the nematode Pristionchus pacificus. Mark Leaver, Merve Kayhan, Angela McGaughran, Christian Roedelsperger, Anthony A Hyman, Ralf Sommer

Disease modelling

Loss of the homologous recombination gene rad51 leads to Fanconi anemia-like symptoms in zebrafish. Jan Gregor Botthof, Ewa Bielczyk-Maczyńska, Lauren Ferreira, Ana Cvejic

Parkin knockout inhibits neuronal development via regulation of proteasomal degradation of p21. Mi Hee Park, Hwa Jeong Lee, Hye Lim Lee, Dong Ju Son, Jung Hoon Ju, Byung Kook Hyun, Sung Hee Jung, Ju-Kyoung Song, Dong-Hoon Lee, Chul-Ju Hwang, Sang Bae Han, Sanghyeon Kim, Jin Tae Hong

Genetic variation and gene expression across multiple tissues and developmental stages in a non-human primate. Anna J Jasinska, Ivette Zelaya, Susan K Service, Christine Peterson, Rita M Cantor, Oi-Wa Choi, Joseph DeYoung, Eleazar Eskin, Lynn A Fairbanks, Scott Fears, Allison Furterer, Yu S Huang, Vasily Ramensky, Christopher A Schmitt, Hannes Svardal, Matthew J Jorgensen, Jay R Kaplan, Diego Villar, Bronwen L Aken, Paul Flicek, Rishi Nag, Emily S Wong, John Blangero, Thomas D Dyer, Marina Bogomolov, Yoav Benjamini, George M Weinstock, Ken Dewar, Chiara Sabatti, Richard K Wilson, J David Jentsch, Wesley Warren, Giovanni Coppola, Roger P Woods, Nelson B Freimer

Genome-wide association study in Collaborative Cross mice reveal a skeletal role for Rhbdf2. Roei Levy, Clemence Levet, Κeren Cohen, Matthew Freeman, Richard Mott, Fuad Iraqi, Yankel Gabet

Drug repurposing for ageing research using model organisms. Matthias Ziehm, Satwant Kaur, Dobril K Ivanov, Pedro J Ballester, David Marcus, Linda Partridge, Janet M Thornton

DYNC1H1 mutations associated with neurological diseases compromise processivity of dynein-dynactin-cargo adaptor complexes. Ha Thi Hoang, Max A Schlager, Andrew P Carter, Simon L Bullock

Tools & resources

No evidence for genome editing of the endogenous DNA in mouse zygotes and HEK293T human cell line using the DNA-guided Natronobacterium gregoryi Argonaute (NgAgo). Nay Chi Khin, Jenna Louise Lowe, Jensen M Lora, Gaetan Burgio

Generating in vivo somatic mouse mosaics with locus-specific, stably-integrated transgenic elements. Gi Bum Kim, Marina Dutra-Clarke, Rachelle Levy, Hannah Park, Sara Sabet, Jessica Molina, Aslam Abbasi Akhtar, Serguei Bannykh, Moise Danielpour, Joshua J Breunig

Highly-efficient Cpf1-mediated gene targeting in mice following high concentration pronuclear injection. Dawn E Watkins-Chow, Gaurav K. K Varshney, Lisa Garrett, Zelin Chen, Erin Jimenez, Cecilia Rivas, Kevin Bishop, Raman Sood, Ursula Harper, William Pavan, Shawn M Burgess

Effective Cell Immunoablation in Undisrupted Developing Avian Embryos. Mariacruz Lopez Diaz, Julia Bujan Valera, Carlos Cadorniga

An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites. Peter J. Skene, Steven Henikoff

Quantitative mRNA Imaging Throughout the Entire Drosophila Brain. Xi Long, Jennifer Colonell, Allan M Wong, Robert H Singer, Timothee Lionnet

grID: A CRISPR-Cas9 guide RNA Database and Resource for Genome-Editing.Vinod Jaskula-Ranga, Don J. Zack

Genetic and transgenic reagents for Drosophila simulans, D. mauritiana, D. yakuba, D. santomea and D. virilis. David Stern, Justin Crocker, Yun Ding, Nicolas Frankel, Gretchen Kappes, Elizabeth Kim, Ryan Kuzmickas, Andrew Lemire, Serge Picard

Single-cell transcriptomes of fluorescent, ubiquitination-based cell cycle indicator cells. Michael Böttcher, Tsukasa Kouno, Elo Madissoon, Efthymios Motakis, Imad Abugessaisa, Sachi Kato, Harukazu Suzuki, Yoshihide Hayashizaki, Takeya Kasukawa, Piero Carninci, Timo Lassmann, Jay Shin, Charles Plessy

Revealing compartmentalised membrane diffusion in living cells with interferometric scattering microscopy. Gabi de Wit, David Albrecht,  Helge Ewers, Philipp Kukura

Second Generation Drosophila Chemical Tags: Sensitivity, Versatility and Speed. Ben Sutcliffe, Julian Ng, Thomas O. Auer, Mathias Pasche, Richard Benton, Gregory S. X. E. Jefferis, Sebastian Cachero

FerriTag: A Genetically-Encoded Inducible Tag for Correlative Light-Electron Microscopy. Nicholas I Clarke, Stephen J Royle

Label-free high-resolution 3-D imaging of gold nanoparticles inside live cells using optical diffraction tomography. Doyeon Kim, Nuri Oh, Kyoohyun Kim, SangYun Lee, Jiho Park, YongKeun Park

Intensity-based axial localization approaches for multifocal plane microscopy. Ramraj Velmurugan, Jerry Chao, Sripad Ram, E. Sally Ward, Raimund J Ober

Resolving Biology Beyond the Diffraction Limit with Single-Molecule Localization Microscopy. [Review] Nafiseh Rafiei, Daniel Nino, Joshua N Milstein

Mindboggling morphometry of human brains. Arno Klein, Satrajit S. Ghosh, Forrest S. Bao, Joachim Giard, Yrjo Hame, Eliezer Stavsky, Noah Lee, Brian Rossa, Martin Reuter, Elias Chaibub Neto, Anisha Keshavan

The Fruit Fly Brain Observatory: from structure to function. Nikul H Ukani, Chung-Heng Yeh, Adam Tomkins, Yiyin Zhou, Dorian Florescu, Carlos Luna Ortiz, Yu-Chi Huang, Cheng-Te Wang, Paul Richmond, Chung-Chuan Lo, Daniel Coca, Ann-Shyn Chiang, Aurel A Lazar

NeuroNLP: a natural language portal for aggregated fruit fly brain data. Nikul H Ukani, Adam Tomkins, Chung-Heng Yeh, Wesley Bruning, Allison L Fenichel, Yiyin Zhou, Yu-Chi Huang, Dorian Florescu, Carlos Luna Ortiz, Paul Richmond, Chung-Chuan Lo, Daniel Coca, Ann-Shyn Chiang, Aurel A Lazar

NeuroGFX: a graphical functional explorer for fruit fly brain circuits. Chung-Heng Yeh, Yiyin Zhou, Nikul H Ukani, Aurel A Lazar

A synthesis of over 9,000 mass spectrometry experiments reveals the core set of human protein complexes. Kevin Drew, Chanjae Lee, Ryan L. Huizar, Fan Tu, Blake Borgeson, Claire D. McWhite, Yun Ma, John B. Wallingford, Edward M. Marcotte

MultiCellDS: a standard and a community for sharing multicellular data. Samuel H. Friedman, Alexander R.A. Anderson, David M. Bortz, Alexander G. Fletcher, Hermann B. Frieboes, Ahmadreza Ghaffarizadeh, David Robert Grimes, Andrea Hawkins-Daarud, Stefan Hoehme, Edwin F. Juarez, Carl Kesselman, Roeland M.H. Merks, Shannon M. Mumenthaler, Paul K. Newton, Kerri-Ann Norton, Rishi Rawat, Russell C. Rockne, Daniel Ruderman, Jacob Scott, Suzanne S. Sindi, Jessica L. Sparks, Kristin Swanson, David B. Agus, Paul Macklin

Paired CRISPR/Cas9 guide-RNAs enable high-throughput deletion scanning (ScanDel) of a Mendelian disease locus for functionally critical non-coding elements. Molly Gasperini, Gregory M Findlay, Aaron McKenna, Jennifer H Milbank, Choli Lee, Melissa D Zhang, Darren A Cusanovich, Jay Shendure

RNAtor: an Android-based application for biologists to plan RNA sequencing experiments. Shruti Kane, Himanshu Garg, Neeraja M Krishnan, Aditya Singh, Binay Panda

Tracking stem cell differentiation without biomarkers using pattern recognition and phase contrast imaging. John Duncan Delaney, Yuhki Nakatake, David Mark Eckley, Nikita V. Orlov, Christopher Edmond Coletta, Chris Chen, Minoru S. Ko, Ilya Gregory Goldberg

Publishing & research practice

Ten simple rules for structuring papers. Konrad P Kording, Brett Mensh

On expert curation and sustainability: UniProtKB/Swiss-Prot as a case study. Sylvain Poux, Cecilia N. Arighi, Michele Magrane, Alex Bateman, Chih-Hsuan Wei, Zhiyong Lu, Emmanuel Boutet, Hema Bye-A-Jee, Maria Livia Famiglietti, Bernd Roechert

On the origin of nonequivalent states: how we can talk about preprints. Cameron Neylon, Damian Pattinson, Geoffrey Bilder, Jennifer Lin

SciLite: a platform for displaying text-mined annotations as a means to link research articles with biological data. Aravind Venkatesan, Jee-Hyub Kim, Francesco Talo, Michele Ide-Smith1, Julien Gobeill, Jacob Carter, Riza Batista-Navarro, Sophia Ananiadou, Patrick Ruch, Johanna McEntyre

When null hypothesis significance testing is unsuitable for research: a reassessment. Denes Szucs, John PA Ioannidis

10 Simple Rules for Sharing Human Genomic Data. Manuel Corpas, Charlotte Whicher, Nadezna V Kovalevskaya, Tom Byers, Amanda A McMurray, Fiona GG Nielsen, Varsha K Khodiyar

Why not…

A magnetic protein compass? Michael Winklhofer, Henrik Mouritsen

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I am Isabel Almudi, a postdoctoral researcher in Fernando Casares’ lab, at the Andalusian Centre for Developmental Biology (CABD) in Seville, Spain. In the lab we are focused on studying the control of organ size and identity during development and evolution.

The lab uses the development of insect eyes to investigate the mechanisms and gene networks that regulate tissue growth and final size. Most of our projects use Drosophila melanogaster as a model, but we have recently established two other systems, Episyrphus balteatus (the marmalade hoverfly) and Cloeon dipterum (a mayfly) to address how these mechanisms have changed during Evolution to give rise to the huge diversity found in insect visual systems.

Cloeon dipterum belongs to the Baetidae family of Ephemeroptera, which together with dragonflies and damselflies (Odonata) form the ancient group Paleoptera. Fossil records date ephemeropterans to the Carboniferous, being these insects the first ones that developed wings. This order has a hemimetabolous development, comprising three different phases: nymph, sub-imago and imago. The Baetidae family of mayflies, including C. dipterum, exhibits a striking sexual dimorphism, consisting in the presence of an extra pair of dorsal eyes in males. Females of this species harbour two different types of eyes: the lateral compound eyes and the three frontal ocelli, typical of insects whereas males also develop a pair of extraordinary enlarged compound eyes called “turbanate” due to their shape (Figure 1).

The mayflies have a life cycle that is divided in two main phases, an aquatic phase and a terrestrial phase. The nymphs are aquatic and they can live for several months in freshwater streams, undergoing several moults until they reach their final size. Then, they emerge from the water as sexually immature subimagos that have to moult once more to acquire their sexual maturity. Thousands of adult individuals form swarms and mate while flying some metres above the water. Finally, the females lay the fertilised eggs onto the surface of the water, where they will develop and later hatch as nymphs. One of the particularities of C. dipterum is that it is one of the few ovoviviparous Ephemeroptera species. Thus, once the adult female lays the eggs, they immediately hatch as tinny swimming nymphs (Figure 2).

Closing the life cycle in the lab was one of the first challenges we encountered. Due to space limitation and lack of infrastructure (we do not have a pond inside the institute to leave a swarm of mayflies mate freely), we have to perform forced copulation with them [1]. We grasp the female by the wings with a pair of forceps and place it in an inverted position. The male is placed against the female allowing direct contact between the external genitalia of both. The male genitalia forceps clasp around the female abdomen and the copula starts. The duration of the matings can vary from few seconds to several minutes (Figure 3). After the mating, we keep the females in a petri dish with some wet paper and wait for 15 days, until the embryos have fully developed inside the female abdomen. It is from this moment that we put the females onto the surface of water to allow them to deliver their offspring. We keep the nymphs in beaker glasses with water and air bubbling. These beakers are inside PET bottles to prevent the subimagos to fly away when they emerge from the water (Figure 4).

A typical day in a mayfly lab starts collecting the subimagos and imagos that have emerged and moulted during the night. These will be the specimens that we will use two days later for our crosses, so we put them in a falcon tube with some wet paper to maintain the humidity. As adults, mayflies do not feed, they lack mouth parts, so we do not need to worry about providing them with some food, we just need to avoid their desiccation. Nymphs, on the contrary, are very voracious. We need to feed them every morning with algae or vegetarian fish food flakes. It is very convenient to be in an institute with several zebrafish and medaka labs, as they are our main algae providers, just by scratching the algae that grow on the surface of the fish tanks. After taking care of the nymphs we can start performing some experiments. Having the culture established in the laboratory permits us to select the nymphs at the appropriate developmental stage to study the ontogeny of the turbanate eye and the genes that are involved in the process.

The techniques we use are not very different from the ones applied in other Evo-Devo and Developmental Biology labs working with well-established model organisms. Therefore, widespread procedures like imaging and gene expression studies are performed on a daily basis with the mayflies. Confocal microscopy and immunostainings are used to study the morphology of the turbanate retina and its associate brain centres along its development. Markers, such as antibodies for proliferation or specific cell types, serve us to investigate growth rates and patterning dynamics of the new organ (Figure 5). We have also generated some tools to investigate gene expression. We are able to search for genes in a transcriptome that we have produced and to look for their spatial expression using in situ hybridization at the desired developmental points. Our next goal is to establish functional tools in order to test the candidate genes we are identifying from our gene expression experiments.

Setting up a new model in the lab presents some challenges, but it will help us to answer many questions regarding the origin and evolution of traits that appeared for the first time in insects, thus, every goal we accomplish is really rewarding and exciting.

References and Notes

1. McCafferty, W.P., and Huff, B.L., Jr. (1974). Parthenogenesis in the mayfly Stenonema fermoratum (Say) Ephemeroptera: Heptageniidae). Entomological news 85, 76-80.
2. Isabel Almudi holds a MSCA IEF 657732 fellowship funded by the H2020 program of the European Commission.

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