As astronomers look up to the sky to analyze the infinite universe, developmental biologists look at life unfolding, revealing itself under the light of the microscope. Stars above us, embryos below, we wonder about the possible worlds hindered from our sight. These reflections took place at “The Marine Biology Laboratory Practical Course in Developmental Biology – Quintay 2020” in Chile, where a total of 18 students from 9 different countries (Argentina, Brazil, Chile, Colombia, Ecuador, India, Mexico, Puerto Rico and Uruguay) met, fascinated with the broad diversity of animals, range of experimental techniques, and the huge quality of faculty available in this course.

Despite the fact that most of us were working with one of a small number of “model organisms”, we had the unusual chance to observe, describe and perform experiments with flatworms, sea urchins, fruit flies, Zebrafish, African frogs, and chicken embryos. It was an intense 2 week-practical and theoretical course at the facilities of the Quintay Marine Research Center (CIMARQ) of the Andres Bello University. This immersive experience right next to the Pacific seashore of Chile, together with a remarkable array of experts in different fields of developmental biology in a friendly environment, encouraged us to explore some of the frontiers and unanswered questions in developmental biology.

The course began with the Drosophila module, coordinated by Profs. Nipam Patel (MBL, USA) and John Ewer (University of Valparaiso, Chile). We were introduced to the basic aspects of invertebrate embryogenesis, genetics, and the powerful impact of the Drosophila model in Developmental Biology. Nipam was a very engaging lecturer, transmitting us the beauty of visualizing embryos under a confocal microscope, and giving us the most useful advice for nice immunostainings: “You just need to Wash! Wash! Wash! …and have faith”. We got stunning expression patterns of Hox genes in Drosophila embryos that will become part of a joint publication with results from previous versions of this course. Next, Nipam introduced us to Evo-Devo, the possibility of exploring evolution through the lens of development, by analyzing the gene regulatory networks that establish the anterior-posterior axis of the crustacean Parhyale hawaiensis in comparison to Drosophila.

In sea urchin module, directed by the Prof. David McClay (Duke University, USA) or Uncle Dave as he would say, we took advantage of the CIMARQ-Quintay red sea urchin facility, learning some of the classical experiments of early embryogenesis and the morphogenetic events occurring during sea urchin gastrulation. Dave provoked us with inspiring discussions about developmental biology, and enchanted us with his passion earned through his many years in this field. His lectures about how sea urchin embryo development has been understood were like hearing a nine year old kid telling you about his favorite Christmas presents.

We continued with Prof. Cecilia Moens (University of Washington, USA), who engaged us with an inspiring talk about the early development of the zebrafish brain, and then guided us through a debate about employing gene editing tools such as CRISPR/Cas9 for dissecting early developmental processes, not only in Zebrafish but in almost all research organisms present in the course. This discussion was insightful since nowadays we have a vast array of tools for manipulating gene expression at our fingertips. We were able to compare the advantages and limitations of each one, highlighting the importance of conducting the proper experimental controls.

In the planarian module, Prof. Alejandro Sanchez-Alvarado (Stowers Institute, USA) challenged us to test the regenerative capacities of planarians. He proposed we perform experiments from different kinds of amputations to even tissue transplants, experiments that we would follow for the rest of the course. But his module projected outside the lecture room and the lab. He took us to the closest beach to CIMARQ to get samples of the living creatures that inhabit the Quintay coast. We were impressed by the rich animal diversity that lived there of a variety of shapes and colors. For some of us, it was the first time that we could see, touch and study marine organisms such as sea stars, snails, anemones and a variety of worms including planarians.

The first week ended with a lecture by Prof. Alfonso Martinez Arias (University of Cambridge, UK) on gastruloids and mouse stem cells. He engaged us in a discussion about the philosophical aspects of developmental biology. “Do you think a machine can be an embryo?” he said, to our astonished faces. These sorts of questions lit a heated debate. We discussed the manipulation of human stem cells and embryos, the possibility to compute embryonic development and the limitations of modeling biological phenomena. A key idea that emerged from the conversation, was that we should start talking about “research organisms” instead of “model organisms” because ultimately a model organism only models itself. The group was surprised and motivated by the questions, and the conversation was inspiring: at the end of the day, nobody was indifferent.

Led by Profs. Sally Moody (The George Washington University, USA), Roberto Mayor (University College of London, UK), and Fernando Faunes (University Andres Bello, Chile) the Xenopus module then came into the picture. After enlightening and fulfilling lectures, the practical activities were free and diverse. We were able to choose from a variety of different experiments to learn about axis development and the dorsal organizer inductive properties in Xenopus. Starting with different practical techniques to manipulate embryos – even using an eyebrow as a tool – we were challenged to graft neural crest cells from a fluorescent donor embryo into a wild-type host embryo. Despite the high handling complexity of this experiment, many of us succeeded and were able to record the neural crest migrating in living embryos. This module ended up with the presentation of our results and a funny awards ceremony.

To conclude the organism modules, Profs. Andrea Streit (King’s College London, UK), Claudio Stern (University College London, UK), and João Botelho (Pontificia Universidad Católica de Chile) guided us through the fascinating world of chick development. In very didactical, histrionic and immersive lectures with Claudio, we studied concepts such as regulative development and cell states during early chick embryo development. Then, Andrea brought our attention to non-coding regulatory regions in DNA and regulation of gene expression in the context of sense organ development. In the laboratory, we did ex ovo culture of primitive streak stage embryos and we injected DiI or DiO in Hensen´s node and could follow cell fates and see a fluorescent notochord the next day. We also did in ovo culture experiments and tried methods such as electroporation, to introduce morpholinos, and adding beads to the embryos to study limb development. Inspired by the organizer transplant experiments in Xenopus we asked to do something similar with chicken embryos. Andrea, who is an expert in node transplantation, quickly taught us this technique and the next day we were able to discuss the inductive capacity of the node according to the region where it had been transplanted.

A week into the course we had the opportunity to attend the “Developmental Biology Symposium-Quintay 2020”. Researchers from different universities of Chile came to Quintay to share their work, integrated with talks of some professors of the course. It was an amazing event to get to know the high quality and engaging science developed in Chile.

During the course, the most important complementary activities were the student talks in the evenings. Here, we had the opportunity to introduce our own research projects to the whole group in a very comfortable and relaxed setting, enjoying drinks and snacks during the presentations. The variety of research organisms was amazing, from Drosophila, Zebrafish, Medaka, C. elegans, passing through Xenopus, Axolotls, and even Cestodes and wild Planarian species. Even the experimental approaches varied from one to another, from molecular biology to very robust bioinformatics. The discussion that came up was very helpful, adding different classical and new approaches that we could use in our projects. On many occasions, it was so interesting that we kept talking about it in our lab nights, where the fun lasted until late and we would finish our experiments and record our results with a confocal microscope, with essential help from Jaime Espina (University Andres Bello).

Although all these activities sound tough and demanding, occasions to give our minds a break and enjoy a relaxed conversation were not missing. Besides the lunch time and student talks, we were able to organize a BBQ with our professors and fellows. Here, we got to know each other better, discuss in a relaxed atmosphere, and why not?, laugh with some jokes and chat about life (our life, not the embryo’s!). Another memorable activity was a visit to a neighboring beach, where together with some faculty we were able to enjoy a nice picnic next to ocean. All of this highlights how engaging this course is, how interaction between students and professors, even outside a purely academic context, lies at its heart.

To close these awesome weeks, the closing ceremony was presided over by Prof. Ángela Nieto (CSIC-UMH, Spain), with a lecture of the most recent findings of her laboratory, including the blended study of gene expression profiles, the physical, and cellular variations controlling normal development, metastasis, and cell proliferation. Afterwards, the professors awarded Ailen Cervino and Nicolas Cumplido with a well-deserved reward, which will enable them to attend the next “Embryology: Concepts & Techniques in Modern Developmental Biology” MBL course. Finally, we had lunch together on the Quintay coast, enjoying such good company and filled with energy, looking ahead for our own goals.

A year has passed since “Quintay 2020” took place, a few months before the Covid-19 pandemic broke out. We didn’t know then how fortunate we were to carry out face-to-face discussions, share the bench with other students and professors, or even enjoy a BBQ with people from all over the world! Even though much effort has been placed in order to continue with courses and meetings online, being able to experience a practical course like this one in real life, we believe, has transcendental effects on its students, both at the personal and professional level. Hopefully, new generations of Developmental Biologists will draw on the “Quintay experience” in the near future.

Students (co-authors) & Talks:

Juan A Sanchez. Growth coordination within tissue in Drosophila.
Felipe Berti Valer. The Irre cell Recognition Module and ovarian development in Drosophila: the role of the Roughest protein.
Marycruz Flores Flores. Characterization of cell recruitment mechanism driven by vestigial in the imaginal wing disc of Drosophila melanogaster.
Alison Julio. Structural aspects and evolutive conservation of Calpain action in early insect embryogenesis.
Pablo Guzman. The Slit/Robo pathway is required in different stages of the development of the Drosophila lobula plate.
Emiliano Molina. Differential requirement of the t6A modification in tRNAs, between undifferentiated and differentiated cells in Drosophila melanogaster.
Emilio Oviedo. Regeneration in Ecuadorian land and freshwater planarians.
Cristian Reyes. Reprimo genes in cancer and development, what do we know so far?
Nicolas Cumplido. From Devo to Evo: Hox genes and the shaping of the zebrafish caudal fin.
Sruthi Purushothaman. Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development.
Aitana Castro Colabianchi. The role of Notch1 during the early development.
Ailen Cervino. A conserved role of Furry in cell polarization and morphogenesis.
Diana Carolina Castañeda Cortés. Crossover between stress and tyroid hormone axes in stress-induced sex reversal.
Felipe Gajardo. Transposable elements in zebrafish hypoxic response: What the data has to tell us.
Oscar Javier Ortega Recalde. DNA methylation memory: Understanding epigenetic reprogramming in vertebrates.
Tonatiuh Molina. Betaglycan, a multifunctional accessory.
Jimena Montagne. Cell differentiation and tissue reorganization during the larval metamorphosis of cestodes.
Juan Rodriguez. Regulation of embryonic cell fate decision by histone methylation.

(8 votes)

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In the latest episode of Genetics Unzipped we’re taking a look at the life of JBS Haldane, whose work, writing and dominant personality made him one of the most interesting characters of 20th century genetics.

As well as being an insightful scientist, fearless self-experimenter and artful communicator, Haldane’s political leanings also affected his approach to science – even at the expense of the scientific rigour that he usually applied to his endeavours.

Kat Arney speaks with Samanth Subramanian, author of the new biography A Dominant Character: The Radical Science and Restless Politics of J.B.S. Haldane to find out more about Haldane’s life, work and complex legacy.

Genetics Unzipped is the podcast from The Genetics Society. Full transcript, links and references available online at GeneticsUnzipped.com.

Subscribe from Apple podcasts, Spotify, or wherever you get your podcasts.

And head over to GeneticsUnzipped.com to catch up on our extensive back catalogue.

If you enjoy the show, please do rate and review on Apple podcasts and help to spread the word on social media. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com Follow us on Twitter – @geneticsunzip

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Yesterday we held the fifth webinar in our series, this time chaired three members of the preLights team – Sundar Naganathan, Irepan Salvador-Martinez and Grace Lim – in celebration of the site’s third birthday.

Below you’ll find recordings of the talks and live Q&A sessions.

Michèle Romanos (from Bertrand Benazeraf’s lab at the Centre de Biologie Integrative in Toulouse)

‘Cell-to-cell heterogeneity in Sox2 and Brachyury expression ratios guides progenitor destiny by controlling their motility.’

Michèle’s preprint can be found here:

https://www.biorxiv.org/content/10.1101/2020.11.18.388611v2

Marc Robinson-Rechavi (University of Lausanne & Swiss Institute of Bioinformatics)

‘The hourglass model of evolutionary conservation during embryogenesis extends to developmental enhancers with signatures of positive selection’

Marc’s preprint, a collaboration with the lab of Eileen Furlong and led by Jialin Liu, can be found here:

https://www.biorxiv.org/content/10.1101/2020.11.02.364505v2

Meng Zhu (from Magdalena Zernicka Goetz’s lab at the University of Cambridge)

‘Mechanism of cell polarisation and first lineage segregation in the human embryo’

Meng’s preprint can be found here:

https://www.biorxiv.org/content/10.1101/2020.09.23.310680v1

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A Research Associate post is available in the Morphological Evolution Research Group led by Emília Santos in the Department of Zoology at the University of Cambridge. The preferred start date is 1^st May 2020. The successful candidate will join a vibrant and inter-disciplinary research environment with an excellent international reputation. They will work as a key member of our research team investigating the genetic and developmental mechanisms underlying organismal diversification.

More specifically, the Postdoctoral Researcher will investigate neural crest cell evolution in cichlid fishes. Neural crest cells are a multipotent embryonic cell population that emerge from the vertebrate dorsal neural tube during early development. They then delaminate and undergo some of the longest migrations of any embryonic cell type to give origin to multiple derivatives such as pigment cells, neurons and glia of the peripheral nervous system, smooth muscle, craniofacial cartilage and bone. Many of the features that distinguish vertebrates from their chordate relatives are derived from the neural crest, making this multipotent embryonic cell population a key innovation central to vertebrate evolution.

The successful candidate will compare neural crest development across different cichlid fish species harbouring variation in neural crest derived traits (e.g. pigmentation patterns and craniofacial skeleton), to determine when and how variation in neural crest developmental mechanisms shapes adult trait morphology in a set of extremely closely related species. The project will involve the use of diverse setof techniques such as in situ hybridisation gene expression assays, live imaging of fluorescent reporter lines, and single cell RNA sequencing.

We are looking for a highly motivated candidate with a strong interest in evolutionary developmental biology, comparative embryology, and genomics. The Department of Zoology has a strong Evolutionary and Developmental Biology group, with researchers working in a variety of different organisms. The Department provides access to state-of-the-art imaging and sequencing facilities. Furthermore, the Research Associate will work in close collaboration with other groups in Cambridge working on cichlid population genomics (Prof. Richard Durbin) and epigenetics (Prof. Eric Miska).

Applications should include a motivation letter, a CV and contact details for at least two referees (more information here https://www.jobs.cam.ac.uk/job/28629/). We are committed to increasing diversity, equity and inclusiveness in STEM and encourage applications from underrepresented groups.

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A postdoctoral research position is available in the laboratory of Dr. Michael Smutny at the Centre for Mechanochemical Cell Biology at Warwick Medical School, UK. The lab is focused on exploring biochemical and biophysical processes driving cell and tissue morphogenesis during early embryonic development. For a brief overview of the research in the lab, please visit https://mechanochemistry.org/Smutny/research/.

The successful candidate will work in a new state-of-the-art Interdisciplinary Biomedical Research Building (IBRB), which is part of a thriving research community at Gibbet Hill Campus including the School of Life Science, Warwick Medical School and the Centre for Mechanochemical Cell Biology.

The focus of the project will be on identifying biophysical and biochemical determinants controlling collective cell migration of embryonic progenitor cells in the zebrafish embryo. The project will investigate molecular and physical mechanisms underlying polarisation and directed cell migration combining a range of in vivo and in vitro approaches. The suitable candidate will use state-of-the-art microscopy, computational image analysis tools, latest techniques in cell/developmental biology (gene/protein perturbations, optogenetics), biophysical methods and have the possibility to establish interdisciplinary collaborations. Full training in new techniques and career development opportunities will be provided.

Highly motivated candidates with a strong background in advanced microscopy, image processing, biophysical approaches and high interest in interdisciplinary and collaborative research are encouraged to apply. Practical experience in working with a model organism (zebrafish, drosophila or similar) is desired, but not essential. Candidates should be able to work independently, have excellent communication and interpersonal skills, and participate in supervision of students.

For more details about the project and how to apply, please visit Warwick jobs (post 103651-0221), or get in touch for enquires and expression of interest directly to michael.smutny@warwick.ac.uk. The application closing date is 8^th March 2021.

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Bioinformatics scientist positions at the postdoctoral level are available in the lab of Dr. Sabine Dietmann at Washington University School of Medicine in St. Louis, Missouri, USA.  Our research program is dedicated the development of multi-omics and machine learning approaches to the data sets generated in stem cell-based model systems for embryonic development and organoids. (https://informatics.wustl.edu/research-lab-sabine-dietmann). The candidate’s independent research will benefit from our lab’s extensive collaborative network in the Department of Developmental Biology and the Division of Nephrology at Washington University in St Louis and at international institutions. Projects are available in the following areas: (1) comparing developmental trajectories across species (2) machine learning models for cell fate decisions and gene regulatory networks (3) epitranscriptomics in single cells (https://profiles.wustl.edu/en/persons/sabine-dietmann).

We are seeking enthusiastic and talented candidates with high proficiency in scientific programming languages, such as R and Python/PERL. A good understanding of machine learning frameworks in Python (Keras/Tensorflow), experience with creating packages in R or some experience with single cell data analysis and genomics would be very beneficial.

Applicants should have a Ph.D. or master’s degree in Biology, Computer Science, Bioinformatics, Physics or related field plus 2 years of demonstrated relevant research experience.

Consistently ranked among the top 10 US medical schools, Washington University School of Medicine offers a highly interactive and stimulating academic environment for scientists in training, a place where you can be an individual and achieve exceptional things. Washington University in St. Louis is an equal opportunity employer and committed to providing a comprehensive and competitive benefits package. Our lab is located in the Central West End of St. Louis, a vibrant neighborhood adjacent to major cultural institutions.

For further information please contact sdietmann@wustl.edu.

To apply for this position please submit a CV, a cover letter describing your research interests and contact information for two references no later than March 14 to sdietmann@wustl.edu.

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The Tavosanis lab welcomes applications for a post-doc position to study the cellular mechanisms of neuronal dendrite differentiation in Drosophila.

For reference, please, see: Stuerner et al., Development 2019 https://doi.org/10.1242/dev.171397; Castro et al. Elife 2020 doi: 10.7554/eLife.60920; Stuerner et al., Biorxiv https://www.biorxiv.org/content/10.1101/2020.10.01.322750v1; Baltruschat et al., Biorxiv https://www.biorxiv.org/content/10.1101/2020.07.07.191064v1).

This project will combine the generation of molecular tools for acute manipulation of protein activity with high-resolution in vivo microscopy.

For more details, please, contact Gaia Tavosanis directly at: gaia.tavosanis@dzne.de

To apply, you can follow the link: https://jobs.dzne.de/en/jobs/50653/postdoctoral-researcher-fmd-1871202011

(2 votes)

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Position Summary:
The Paul Lab at the MBL seeks a highly motivated individual to join the Josephine Bay Paul Center for Comparative Molecular Biology and Evolution as a Research Assistant (Level I). The successful candidate will be responsible for carrying out routine laboratory work as outlined below. Our research group is looking at the processes that diversify microbial genes, to better understand the functional significance of protein variation in cells and viruses from a variety of biomes.

Additional Information:
The primary aim of the position is to maintain the molecular lab facilities and to assist in developing genetic experiments with bacteria/archaea primarily derived from marine and freshwater ecosystems. Responsibilities will include establishing and monitoring cell cultures, maintaining lab equipment, ordering lab supplies, and conducting basic molecular experiments.

Basic Qualifications:
A Bachelor’s degree in biology, molecular biology or a related discipline is required. This position requires an independent, organized, and self-motivated individual with strong problem-solving skills and the ability to multitask. Prior experience in a research lab and applying basic molecular biology techniques is required. Excellent written, verbal, and interpersonal skills; attention to detail; and a strong work ethic are essential. Position level and salary will depend upon education and experience.

Preferred Qualifications:
The ideal candidate will have prior experience with nucleic acid purification, PCR, and maintaining (bacterial/archaeal) cell cultures.  An understanding of basic molecular biology concepts is important.

Physical Requirements:
Minimal exposure to biohazardous chemicals. Occasional lifting of heavy objects.

Required documents:
Apply on the MBL website and include the following documents in your application package: cover letter, resume/CV, copies of most recent transcripts (unofficial is acceptable), and contact details of 3 references.

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By Oriana Q. H. Zinani, Kemal Keseroğlu, Ahmet Ay & Ertuğrul M. Özbudak:

Gene expression is an inevitably stochastic process (Ozbudak et al., 2002). In contrast, embryonic development and homeostasis require cells to coordinate the spatiotemporal expression of large sets of genes. Many mechanisms are known to orchestrate this coordination, such as operons, bidirectional promoters, enhancer sharing, 3-D DNA looping, topologically associated domains, transcription factories or hubs, and shared upstream regulators.

In metazoans, pairs of co-expressed genes often reside in the same chromosomal neighborhood, with gene pairs representing 10 to 50% of all genes, depending on the species (Adachi and Lieber, 2002; Arnone et al., 2012). Although many paired genes encode for essential housekeeping proteins, some encode for signaling regulators and transcription factors (such as CYP26A1–CYP26C1, ETS1–FLI1, MRF4–MYF5, MESP1–MESP2, SIX1–SIX4–SIX6, and STAT1–STAT4), which have transcription start sites that are 9–516 kb apart. Because various other mechanisms can ensure correlated gene expression, the selective advantage of maintaining adjacent gene pairs remains unknown.

To address this question, in Zinani et al, we used two linked zebrafish segmentation clock genes, her1–her7, as the testbed. The subdivision of the anterior–posterior axis into a fixed number of somites is a landmark example of how coordinated gene expression patterns the vertebrate embryo. During somitogenesis, groups of cells synchronously commit to segmentation in a notably short time frame. The pace of segmentation is set by the period of an oscillator, the segmentation clock, in cells of the unsegmented presomitic mesoderm (PSM). Oscillatory expression of the Hes or her clock genes is conserved in vertebrates; disruptions of their oscillations lead to vertebral segmentation defects (i.e., congenital scoliosis in humans). Approximately every 30 min in zebrafish, around 200 cells bud from the PSM to form a new somite. Segmentation is carried out for a species-specific number of cycles (33 in zebrafish). Her1 and Her7 are basic helix-loop-helix (bHLH) proteins that dimerize to bind DNA. The zebrafish segmentation clock relies on a transcriptional negative-feedback loop in which Her7-Hes6 hetero- or Her1-Her1 homodimers repress transcription of her1 and her7 (Ay et al., 2013; Giudicelli et al., 2007; Schroter et al., 2012). In zebrafish, two paired clock genes (her1 and her7) are separated by a 12-kb regulatory intervening sequence. her1 and her7 have similar transcriptional time delays (Hanisch et al., 2013) and RNA half-lives (Giudicelli et al., 2007); therefore, the transcription of her1 and her7 is mainly concomitant in the tissue. To achieve the rapid tempo and reproducible precision of segmentation, the transcription of her1 and her7 should be tightly coordinated.

Chromosomal adjacency was previously shown to cause correlated expression of synthetic reporters (Becskei et al., 2005; Fukaya et al., 2016; Raj et al., 2006). To test the role of gene pairing on transcriptional co-firing, we detected nascent transcription loci in the nucleus of single cells with single-molecule fluorescence in situ hybridization (smFISH) (Keskin et al., 2018; Zinani et al., 2021). We found that the probability of transcriptional co-firing of paired her1 and her7 genes on the same chromosome is significantly higher than the two unpaired her1 genes on homolog chromosomes. This finding demonstrated that gene pairing augments correlated transcription of the two clock genes by triggering transcriptional co-firing.

Co-firing of two paired clock genes could be advantageous for somite segmentation as it would coordinate transcript levels. To test this hypothesis, we generated cis and trans double heterozygous embryos by using CRISPR/Cas9 (Figure). The cis heterozygous mutants carried two mutant genes in one chromosome and two wild-type genes on the homologous chromosome (Figure, top row). In contrast, the trans mutants carried a mutant her1 gene adjacent to a wild-type her7 gene on one chromosome, and a mutant her7 gene adjacent to a wild-type her1 gene on the other chromosome (Figure, bottom row). Hence, fish that are compound heterozygous for these alleles will have the same functional gene dose as the previously described double heterozygous embryos with paired her1 and her7 genes (Figure, left column). We next raised the gene-paired and gene-unpaired embryos at 21.5 °C, where wild-type embryos successfully form somites. Gene-unpaired embryos had reduced success in somite segmentation as compared to gene-paired embryos (Figure, right column). These results revealed that maintaining paired genes in the genome is beneficial for successful pattern formation during embryonic development.

We next investigated the mechanism by which gene pairing is beneficial for clock oscillations. Although negative-feedback loops are widespread in gene regulatory networks, they usually do not give rise to oscillations, but instead act as a rheostat to tightly maintain gene expression around a steady-state. For a negative-feedback loop to generate oscillations, several important criteria need to be satisfied. Previous studies revealed the importance of time delays and short RNA or protein half-lives to generate sustained oscillations. However, another important criterion needed to generate oscillations is that the rate of transcription needs to be high enough to push the system into an unstable steady-state, establishing a limit cycle (Lewis, 2003; Novak and Tyson, 2008). We found that when genes are paired on the same chromosome, co-transcription happens more frequently. We hypothesized that co-firing of transcription results in a high rate of RNA production, and thereby overshoots the limit-cycle threshold. Simulations of our stochastic model agreed with our hypothesis.

To assess the function of gene pairing in the segmentation clock in real-time, we imaged transgenic Tg(her1:her1-Venus) (Delaune et al., 2012) zebrafish embryos along the entire PSM. We quantified the amplitude of oscillations in the next presumptive somites for 11 somite cycles. We found that the average amplitude was decreased in gene-unpaired embryos compared to gene-paired embryos. The amplitudes of oscillations preceding disrupted boundaries were significantly lower than the ones preceding the successful ones in a given genetic background.

Our results demonstrate that the prevention of gene pairing disrupts oscillations and segmentation in zebrafish embryos. We predict that gene pairing is similarly advantageous in other biological systems, and our findings could inspire engineering of precise synthetic clocks in embryos and organoids.

References:

Adachi, N., and Lieber, M.R. (2002). Bidirectional gene organization: a common architectural feature of the human genome. Cell 109, 807-809.

Arnone, J.T., Robbins-Pianka, A., Arace, J.R., Kass-Gergi, S., and McAlear, M.A. (2012). The adjacent positioning of co-regulated gene pairs is widely conserved across eukaryotes. Bmc Genomics 13.

Ay, A., Knierer, S., Sperlea, A., Holland, J., and Özbudak, E.M. (2013). Short-lived Her Proteins Drive Robust Synchronized Oscillations in the Zebrafish Segmentation Clock. Development 140, 3244-3253.

Becskei, A., Kaufmann, B.B., and van Oudenaarden, A. (2005). Contributions of low molecule number and chromosomal positioning to stochastic gene expression. Nature genetics 37, 937-944.

Delaune, E.A., Francois, P., Shih, N.P., and Amacher, S.L. (2012). Single-cell-resolution imaging of the impact of notch signaling and mitosis on segmentation clock dynamics. Dev Cell 23, 995-1005.

Fukaya, T., Lim, B., and Levine, M. (2016). Enhancer Control of Transcriptional Bursting. Cell 166, 358-368.

Giudicelli, F., Ozbudak, E.M., Wright, G.J., and Lewis, J. (2007). Setting the Tempo in Development: An Investigation of the Zebrafish Somite Clock Mechanism. PLoS Biol 5, e150.

Hanisch, A., Holder, M.V., Choorapoikayil, S., Gajewski, M., Ozbudak, E.M., and Lewis, J. (2013). The elongation rate of RNA Polymerase II in the zebrafish and its significance in the somite segmentation clock. Development 140, 444-453.

Keskin, S., Devakanmalai, G.S., Kwon, S.B., Vu, H.T., Hong, Q., Lee, Y.Y., Soltani, M., Singh, A., Ay, A., and Ozbudak, E.M. (2018). Noise in the Vertebrate Segmentation Clock Is Boosted by Time Delays but Tamed by Notch Signaling. Cell reports 23, 2175-2185 e2174.

Lewis, J. (2003). Autoinhibition with transcriptional delay: A simple mechanism for the zebrafish somitogenesis oscillator. Current Biology 13, 1398-1408.

Novak, B., and Tyson, J.J. (2008). Design principles of biochemical oscillators. Nat Rev Mol Cell Biol 9, 981-991.

Ozbudak, E.M., Thattai, M., Kurtser, I., Grossman, A.D., and van Oudenaarden, A. (2002). Regulation of noise in the expression of a single gene. Nat Genet 31, 69-73.

Raj, A., Peskin, C.S., Tranchina, D., Vargas, D.Y., and Tyagi, S. (2006). Stochastic mRNA synthesis in mammalian cells. Plos Biology 4, 1707-1719.

Schroter, C., Ares, S., Morelli, L.G., Isakova, A., Hens, K., Soroldoni, D., Gajewski, M., Julicher, F., Maerkl, S.J., Deplancke, B., et al. (2012). Topology and dynamics of the zebrafish segmentation clock core circuit. PLoS Biol 10, e1001364.

Zinani, O.Q.H., Keseroglu, K., Ay, A., and Ozbudak, E.M. (2021). Pairing of segmentation clock genes drives robust pattern formation. Nature 589, 431-436.

(6 votes)

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In our third SciArt Profile we meet Sydney Wyatt, a PhD student based at the University of California, Davis.

Where are you originally from, where do you work now, and what do you work on?

I am originally from a small Northern California town, Paradise. I went out of state to get my BS at University of Utah in Salt Lake City, and while I enjoyed my time there, I’m happy to be pursuing my PhD in Integrative Genetics and Genomics at University of California, Davis; it gives me the opportunity to be closer to my parents. My thesis research in Dr. Bruce Draper’s lab currently revolves around interrogating sex determination and early gonad development in zebrafish. Specifically, I am investigating the female sex determination pathway, as well as the role of gap junctions in early germ cell development.

Has science always been an important part of your life?

I remember loving dinosaurs growing up: my favorite is still Parasaurolophus. Understandably, I wanted to be a paleontologist for a long time, although it changed to forensic pathologist by the time I went to college. After my first anatomy lab I quickly changed my mind! Instead, I found I loved genetics and developmental biology through my classes and undergraduate research. Despite working on specific projects now, I still enjoy learning about other fields (and still love learning about dinosaurs!).

I was fortunate that STEM was always encouraged by my family, despite limited exposure growing up. I didn’t have access to the opportunities and mentorship I volunteer for today, namely mentoring high school senior research projects and various public science outreach events like the North Bay Science Discovery Day. I think if I had had those opportunities, I might have learned what I wanted out of my education more quickly.

And what about art – have you always enjoyed drawing/painting/etc?

I was a ballet dancer for many, many years, so performing arts were important to me. I didn’t start drawing until high school when I needed a new creative outlet after an injury. I took classes from a local oil painter, and he mentored my senior community project. I eventually moved into digital art; it allows me to do my art in short bursts in any location without hauling around a pad of paper and a case of pencils. It’s nice to have that outlet to help me avoid burnout.

“Digital art allows me to do my art in short bursts in any location”

What or who are your artistic influences?

I have been drawing a lot of fish lately thanks to my pandemic discovery of #SundayFishSketch created by Rene Martin on Twitter.

How do you make your art? 

I pick a subject based either on suggestions from friends and family or a color palette. I try to vary the main color to avoid too much repetition. Varying the subject helps too: I rotate between fish, flowers and birds. Once I have my subject and references, I get sketching. For physical pieces, I use a grid technique to help me capture the relative positions of all the details. For digital pieces, I start with basic shapes (and use the eraser and undo button a lot). Color swatching is important. I’ll do a couple practice swatches to warm up and remind myself of what I was thinking when designing the piece. The main colors get lightly blocked first with shadows and highlights, and then I build up from there. I have a tendency to do entire sections in one sitting, like one entire wing of a bird, to keep my technique consistent.

Does your art influence your science at all, or are they separate worlds?

I work on fish, so maybe a little influence. There are a couple of zebrafish-themed Sunday fish sketches floating around Twitter. Science I read about influences my art, too. I learned about really interesting killifish genomics research and was inspired to create a whole series of non-traditional model organisms, like killifish or gar or delta smelt. These organisms are so important but not widely heard of outside their niches.

What are you thinking of working on next?

I’m excited to keep working on my research projects, as well as continue to build my art and writing portfolios. As far as art goes, I’ve recently been commissioned by friend to help make label for a home-brewed beer called Axolotl Ale. I also manage a sticker shop (mostly fish) based on previous interest in purchasing pieces. My long-term goal is continue to create non-traditional model organism pieces to highlight the diversity in research subjects for the public as part of my science communication efforts.

Zebrafish: This quick painting was 100% inspired by my research—I work with zebrafish as my model organism.

Killifish: I learned about killifish as a model organism in toxicology and aging research only recently. Specifically, the African turquoise killifish is up-and-coming in aging research. For this piece I wanted to play up the deep blues and purples I saw in my reference images.

Three-spined Stickleback: My college evolution and development professor had done research on these fish, and working on this piece inspired me to start my collection of model organisms less well known to the public.

Pacific Spiny Lumpsucker: This is the piece that started my sticker shop. A friend commissioned me to make this for stickers. People were interested in where they could get their own PSL stickers and I opened my shop.

Medaka: This was another sticker commission for a friend who uses these as her model organism in toxicology research.

Mandarin Fish: This was one of my earlier #SundayFishSketch pieces. It took me two weeks to get all the details right! Since then, I do quicker pieces for the prompts and more elaborate ones for myself or commissions.

Fish Gallery (click for full size image & caption)

We’re looking for new people to feature in this series throughout the year – whatever kind of art you do, from sculpture to embroidery to music to drawing, if you want to share it with the community just email thenode@biologists.com (nominations are also welcome!).

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