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To conference or to unconference… a little report of the Institut Pasteur/Qbio symposium MeMoDEvo (Mechanics Morphogenesis Development and Evolution) and its experimental format

Posted by , on 16 January 2023

The diversity and complexity of shape in uni- and multicellular organisms has long been a source of fascination and interrogation. Since the seminal work of D’Arcy Wentworth Thompson, the study of the emergence of shape, so called morphogenesis, has been strongly influenced by the concept of emergence whereby complex pattern/shape can be explained by relatively simple mechanical and mathematical laws. In parallel, the rapid progress of the biochemical characterisation of the regulators of cell signalling has opened the possibility to compare developmental programs and dissect the molecular basis of evolution. Yet, how mechanics and mathematical laws may constrain the evolution of new shapes and morphogenesis has only come back to light recently. For two days (12 and 13th of December 2022), the symposium MeMoDEvo taking place in Institut Pasteur in Paris tried to discuss this issue by gathering interdisciplinary speakers and participants on site and online and organising two mornings of open discussions. The discussions and talks covered a large range of approaches (mathematics, fluid mechanics, soft matter physics, genetics, evolution, developmental biology, epistemology…) showcasing a diverse set of organisms, from mammals, birds, reptiles, insects,  choanoflagellates, plants, algae, yeasts, and bacteria.

This fully hybrid meeting gathered close to 100 participants on site (mostly from Europe) and 100 participants online and its unusual format led to very interesting discussions and interactions. The conference was possible thanks to the support of several sponsors, including The Company of Biologists, the French Society of Developmental Biology, the Qbio initiative in Pasteur and the Pasteur Institute, as well as the DIM Elicit initiative

“Unconference” morning sessions and open discussions

One of the best parts of conferences that we had been missing over the past two years is the free time and open discussions in between sessions. We therefore dedicated a significant amount of time to open discussions and round tables during mornings with a subset of participants and the speakers (roughly 40 people). In line with the spirit of the meeting, we relied on a mixture of programmed schedule and self-organization.This engaging time involved first a quick introduction by each participant on their background and interest, followed by open discussions on the first day. This was followed the next morning by three round table discussions.

The first round table addressed constraints on the evolution of shape and how to reveal them experimentally. How can an organ evolve from one shape into another? Are there any limitations regarding shape innovation? The discussion included the distinction between pure physical/environment constraints and developmental hard-wired constraints related to the evolution history of the organism. Exploring the distribution of organ shape in the morphospace (using landmarks and dimension reduction) using intra and inter-specific variability can reveal such constraints by looking at non-occupied zones in the morphospace. The cause of these unoccupied areas can be either selective pressure or funnelling of evolutionary change by developmental constraints. A combination of description of natural variation and exploration of shape variability in the laboratory (including direct perturbation of developmental processes by mutagenesis and experimental evolution) may help to disentangle them. The discussion ended (as expected) with more questions than answers concluding on the  mysterious cases of abrupt shape evolution/innovation which have to bypass strong developmental constraints while maintaining proper adaptation.

The second discussion was centred on the emergence of multicellularity comparing a large range of organisms which combine single cell and aggregate life mode. By comparing the mode of multicellularity (clonal/aggregative), the signals/conditions triggering aggregation or dissociation and the components that can structure and organise the aggregates (adhesion, contractility, matrix), a very complex pictures emerge with all sort of combination of strategies found in nature, outlining again the diversity of evolutionary path leading to multicellularity (see the table below summarising the comparison).

Finally, the last discussion was centered on sharing experience with various methodologies for mechanical simulation of tissues, ranging from continuous model, object based modeling and finite element modeling.

Afternoon hybrid sessions

The two afternoon sessions were following a more classic conference format alternating talk on site and online with an hybrid crowd. You will find hyperlinks connected to the published works that were discussed during these sessions (preprint and peer-reviewed articles). The meeting was launched by Thibaut Brunet (Institut Pasteur) who made a quick historical overview of the evolution of approaches to understand development and the various phases that brought to the front stage the role of mechanical constraints in shape evolution and its recent rejuvenation. The first talk was then given by Bruno Vellutini from Max Planck CBG who illustrated how the appearance of the cephallic furrow during evolution in Drosophila embryo may have helped to buffer mechanical constraints generated by ectoderm movements and cell division during gastrulation. Marie Monniaux, from the ENS RDP lab in Lyon, described the morphogenesis of petunia petals and sepals and how the comparison of mutants can help to disentangle the regulation of growth and shape by different epidermal layers. Jean-Léon Maître from Institut Curie then provided a quantitative comparison of the mechanisms of embryo compaction in different mammals, illustrating how qualitatively similar mechanisms can yet rely on quite different absolute mechanical properties. Arghyadip Mukherjee from the ENS in Paris described how topological transition through different modes of epithelial fusion can help to describe neuroepithelial organoid shape evolution. This was followed by Jose Bico, from the ESPCI, who illustrated how living matter can be used as an inspiration for generating complex inflatable shape based on local differences of inflation/growth (with a live illustration on stage with cup, saddle or helix shape generating devices). We then came back to insects with Steffen Lemke (from Heidelberg University) who compared gastrulation between different fly species (including Drosophila) and identified essential genes sufficient to explain several morphogenetic innovation in flies (including the mode of mesoderm invagination, cell elongation and the requirement for cephalic furrow). We then finished the first afternoon session with Annemiek Cornelissen from LMSC laboratory in Université Paris Cité,  who used cracking theory and differential mechanical properties of tissues to explain the morphogenesis of jellyfish canal network.

The second afternoon session started with Arkhat Abzanof  from Imperial College London who illustrated the power of morphospace analysis for the understanding of craniofacial shape evolution in vertebrates (from bats, Darwin finches and crocodiles). He was then followed by Hélène de Maleprade from Sorbonne Université who described various collective and single cell swimming strategies in Chlamydomonas, Volvox and Gonium. We then had an online talk from Lakshminarayanan Mahadevan from Harvard university describing fluid mechanics model of multicellular movements occurring during chick gastrulation and how the variation of initial conditions can recapitulate different modes of gastrulation across Vertebrates. This was followed by conceptual and theoretical considerations from Ana Soto and Maël Montevil from the Centre Cavaillès on the concept of autonomy in living systems and the definition of core principles (default state, variation and organisation) allowing proper understanding of a living system. We then came back to plants with Etienne Couturier from the LMSC lab who applied the Lockhart model (describing cell growth as a function of turgor pressure and viscoelastic deformation of the wall) to describe the dynamics of maïze root growth against a physical obstacle. This was then followed by an online talk from Peter Yunker from Georgia Tech describing his work in collaboration with Will Ratcliff on the ‘long-term experimental evolution’ of multicellular development in yeast. Remarkably, experimentally evolved yeast colonies were recently reported to have acquired macroscopic sizes after years of selection in the lab. The talk dissected the cellular and physical basis of this transition, which turned out to rely on mutations promoting elongated cell shape and reducing the mechanical stress that can cause colony fission. The meeting ended with a broad theoretical view of the evolution of multicellularity and morphogenetic innovation by Stuart Newman from New York Medical College, introducing the concept of dynamical pattern modules (integrating gene regulatory network and associated physical/spatial constraints) and their contribution to developmental and morphological innovation during evolution.

Conclusion: a lively and environmentally friendly format promoting discussions and connections

The meeting managed to gather a diverse crowd leading to a very refreshing and eclectic program. The relative “self-organisation” of the morning sessions actually led to very vivid interactions and deepening of the questions related to the meeting topic. All the participants came to conclusion that we should be ready for a MeMoDEvo#2 ! Of note, the symposium was the living proof of the possibility to organise a diverse, inclusive and very dynamics meeting while limiting environmental impact. Every speakers used the train to commute to the meeting and we could yet gathered a diverse crowd from Europe as well as many online attendees and speakers from other continents. Despite the usual technical hiccup associated with the hybrid format, we can only recommend the application of the same recipe !

Romain Levayer, Thibaut Brunet, Katja Heuer and Roberto Toro, organisers of the MeMoDEvo symposium.

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Development presents… a webinar on theoretical and computational modelling of developmental biology

Posted by , on 16 January 2023

Card containing details of the webinar.

Wednesday 25 January 2023 – 15:00 GMT

Our next Development presents… webinar will be chaired by Associate Editor Paul François (who recently moved to the University of Montreal from McGill University). Paul has invited three talks on the topic of theoretical and computational modelling of developmental biology.

Kirsten ten Tusscher (Professor of Computational Developmental Biology at Utrecht University)
‘Reverse engineering lateral root formation’

Simon Freedman (Senior Bioinformatics Scientist at Illumina presenting Postdoctoral work from Madhav Mani‘s group at Northwestern University)
‘A dynamical systems approach to cell fate decisions’

Mindy Liu Perkins (Postdoctoral Fellow in Justin Crocker‘s lab at EMBL)
‘A bistable autoregulatory module in the developing embryo commits cells to binary fates’

The webinar will be held using Zoom with a Q&A session after each talk.

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Gordon Research Conference: Development Biology 2023

Posted by , on 13 January 2023

June 25 – 30 Mount Holyoke College, Massachusetts, USA

It’s back! After 4 years and a global pandemic, the Developmental Biology GRC is on.

This is the premier, international scientific conference for the presentation of cutting-edge and unpublished developmental biology research. The format prioritises discussion and informal interactions among scientists of all career stages after talks, at poster sessions, and during the meeting. We have a great range of speakers, concentrating on the latest developments in the field.

Registration and abstract submission is open:

https://www.grc.org/developmental-biology-conference/2023/

Full speaker list and venue details are also available on the website.

Developmental Biology covers molecular, cellular, tissue and organismal levels, as well as theoretical concepts from physics and mathematics. The 2023 Gordon Conference topics include metabolic fluxes in development, transgenerational inheritance, gene regulation, dynamics of signaling at tissue scale, lineage tracing in the single-cell era, regeneration and tissue mechanics. We have also included a session highlighting the relevance of Developmental Biology to the development of diseases later in life. Because progress in Developmental Biology depends on cross-fertilization of ideas from complementary organisms, presentations will include studies in standard invertebrates such as Drosophila and C. elegans, classic vertebrate models including zebrafish, Xenopus and the mouse, as well as plants, non-classical models and humans. Afternoons and late evenings will be reserved for presentation of posters and informal interactions. The relaxed atmosphere and the rural setting of the meeting will encourage stimulating discussions between established and junior investigators in all aspects of the field.

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PhD and 3year-POSTDOC calls OPEN to come to University of Barcelona

Posted by , on 12 January 2023

Our lab is seeking PhD and POSTDOC candidates to apply to various calls that are NOW OPEN, so hurry up and do not miss any of these opportunities and contatct us ASAP if you are interested in the fields of Genomics, Embryo Development, Bioinformatics, Evolution and Molecular Ecology.

Our lab currently has different research lines ranging from muscle and heart development and the evolutionary impact of gene loss (see an example https://go.nature.com/3E83Lw8), as well as EcoEvoDevo investigations studying the genetic response of the defensome of marine embryos to environmental threats such as biotoxins produced by harmful algal blooms of diatoms in the context of global warming or the effect of noise contamination from human activities on embryo development of marine invertebrate species (see an example in https://go.nature.com/2O82VY8).

Our research focus on the study of the appendicularian tunicate specie Oikopleura dioica as our favourite animal model (see this “A day in our lab” post in the node https://thenode.biologists.com/day-life-oikopleura-lab/lablife/ and embryo microinjection, CRISPR, RNAi, DNAi, fluorescent and confocal imaging, RNAseq, ATACseq, population genomics and bioinformatics are among the techniques we use in our lab. Among candidate postdocs, experience in some of those techniques will positively considered, and specially candidates willing to develop new tools based on CRISPR, as well as candidates willing to develop single-cell omics approaches to Oikopleura dioica to address some of the topics we currently work in the lab or new questions that candidates might be interested.

For PhD, there are varios calls already open, so please contact us as soon as possible, since the dealine is very soon.

For POSTDOCS, there is a call for a 3-year position to be open next week (required to have defended the PhD between 1/1/2021 and 31/12/2022; 30.000 EUR/year), and some other calls are coming in the next moths, some including starting-grants.

CONTACT: Interested candidates, please send an email ASAP to Cristian Cañestro (canestro@ub.edu), including a brief letter of interest, a brief CV, including list of publications with their impact, and technical skills all together in ONE single pdf file.

More info please visit our web: http://goo.gl/0ZaDm0

Recent publication from our lab about massive gene losses and the deconstruction of the cardiopharyngeal gene regulatory network in appendicularians and the origin of the free-living and sessile styles in ancestral tunicates that was highlighted in the cover of nature
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Genetics Unzipped: Baby brain, baby body: The genetics (and epigenetics) of reproduction

Posted by , on 12 January 2023

Pregnant woman

“The placenta is unique amongst organs in that you have two individuals contributing to a single organ.”

Dr Courtney Hanna

In the latest episode of the Genetics Unzipped podcast, we’re going back to the womb to explore the genetics of how to make babies – from finding out how birthweight is linked to the risk of diabetes to investigating the multifaceted role of the hormone prolactin in pregnancy and the role of epigenetics in the placenta.

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.

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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Call for Nominations: 2023 IZFS George Streisinger & Chi-Bin Chien Awards

Posted by , on 11 January 2023

Dear Zebrafish Community,

The International Zebrafish Society (IZFS) is pleased to announce the call for nominations for our two prestigious annual awards – The George Streisinger and the Chi-Bin Chien Awards. Members of the zebrafish community are invited to submit nominations by February 2, 2023. 

About the Awards

The George Streisinger Award recognizes senior investigators in the zebrafish community who have made outstanding and continued contributions to the advancement of the field.

Among the criteria that may be considered:

  • Contributions in the form of conceptual advances that have opened important new research directions
  • Development of tools or resources that have been transformative in enabling new research possibilities
  • Service to the Zebrafish research community

Nominations should be submitted by e-mail with the subject line “George Streisinger Award” to info@izfs.org. The email should include a single PDF file that contains:

  1. A statement (up to one page) written by the nominators describing the key contributions of the nominee to the field.
  2. The statement must be co-signed by two or more IZFS members who support the nomination.
  3. A list of up to ten publications or links to online resources or databases that illustrate the central contributions of the nominee to the field.

The Chi-Bin Chien Award recognizes outstanding graduate students, postdoctoral trainees, or recently appointed faculty members from any country who have made significant contributions to the field of zebrafish research and have exhibited the generosity and openness that characterized and motivated Chi-Bin Chien.

Mentors of PhD or post-doctoral trainees of the zebrafish community are invited to submit nominations for the Chi-Bin Chien Award.

Nominations should be submitted by e-mail with the subject line “Chi-Bin Chien Award” to info@izfs.org. The email should include a single PDF file that contains:

  1. A one-page statement from the nominee describing his/her research and its importance to the advancement of zebrafish research.
  2. The nominee’s CV
  3. Letter of recommendation from the mentor.
  4. Letter of recommendation from one additional scholar who is familiar with the research being described in the application
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Your favourite Development cover is…

Posted by , on 11 January 2023

We asked you to select your favourite Development cover from 2022* and after all the votes were counted, the Node community has chosen the mouse lung lobe from Issue 21. The image is linked to the Open Access Research Article from Prashant Chandrasekaran, Nicholas Negretti, Aravind Sivakumar, Jennifer Sucre, David Frank and colleagues on the role of CXCL12 in defining lung endothelial heterogeneity and promoting vascular growth. 

Issue 21: Mouse lung lobe

In second place were the astrocytic cells in the mouse spinal cord from Maria Micaela Sartoretti, Carla Campetella and Guillermo Lanuza featured on Issue 15. Third place went to the Arabidopsis hypocotyl graft junction from Phanu Serivichyaswat, Kai Bartusch ,Charles Melnyk and colleagues in Issue 5.

Interestingly, it wasn’t any of these entries that won the in-house team at Development the box of chocolates on offer for the most popular cover from The Company of Biologists in 2022. In this competition, the winning cover image was the stages of Xenopus development from Natalya Zahn, Christina James-Zorn, Aaron Zorn and colleagues in Issue 14.

Issue 14 © 2022 Natalya Zahn

Congratulations to the winners and thanks to everyone who submitted cover art in 2022. We are delighted to have had another year filled with wonderful cover images and we are now looking forward to seeing what 2023 brings!

* Issue 24 is from 2021

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BSDB Gurdon Studentship Report – Paula Richter

Posted by , on 10 January 2023

NRAP H100Q Mutation in Zebrafish

During the first year of my course in biological sciences, I became interested in developmental biology. I am mesmerized by the exploration of the beginnings of life through the complex interactions and changes that are taking place from the moment of fertilization. Furthermore, I realized the potential applications that scientific advancements in this area may have for disease prevention and treatment. This is especially interesting to me as a wildlife health student, aiming to conduct research on wildlife conservation in the future.

Research led by Dr. Denis Larkin found a mutation in the amino acid sequence (AA) of the NRAP gene in Yakut Cattle, resulting in a single nucleotide polymorphism (SNP resulting in a Glutamine to Histidine substitution (H100Q) at position 100) (Larkin et al., 2021). Yakut cattle are resistant to the low temperatures of the Siberian arctic and exhibit features such as efficient thermoregulation, a slow metabolic rate, and resistance to diseases. Nebulin-Related-Anchoring Protein (NRAP) is an actin-binding gene responsible for producing proteins to connect actin filaments in skeletal and cardiac muscle (GeneCards, 2022). The NRAP gene AA sequence is evolutionary conserved, however, this specific H100Q mutation was found in other cold-adapted, hibernating species and those entering periods of extreme bradycardia.

The expression of this particular SNP in those specific animal species prompted us to start this study. My summer project aimed to create the H100Q NRAP single-point mutation in the human gene and clone it into a suitable vector for in-vivo expression. This construct will then be used for microinjections into zebrafish embryos to observe potential changes in their heart development, heart rate, and muscle function.                                                                       

I was keen to start the project and started by gathering information about zebrafish heart development, as well as molecular biology techniques. Together with my team, we created a well-thought-out cloning and mutation strategy to substitute a single nucleotide from the human NRAP gene from CAC (H) to CAA (Q) to recreate the H100Q mutation found in Yakut cattle.

However, I soon learned that theory and practice are two very different sides of the same coin. The world of molecular biology seemed to be unpredictable at first! After the first couple of ligations that didn’t produce any colonies, it was difficult to believe that getting enough material to mutate this gene was even possible. But that didn’t stop us. We troubleshot, experimented with enzymes and buffers, made our own competent cells and bacteria plates, changed reaction conditions, consulted papers, and of course, could always rely on the advice of our helpful supervisors. Having an amazing and experienced team around us at all times was key to our success. Not only could they provide valuable insights through their many years of experience in molecular biology but also offered constant encouragement: “it will be fine” turned out to be right. I was determined to make it work and this experience strengthened my resilience and problem-solving skills.

I acquired many useful laboratory skills which will be very invaluable as a researcher. I learned how to read vector maps, how to clone, use publicly available software, and how to design primers for PCR… just to name a few. Understanding the science behind molecular biology techniques allowed me to modify protocols to troubleshoot efficiently. Finally, the Sanger-sequencing results came back, and excitingly, we validate our single-point mutation H100Q of the human-NRAP gene in pBluescript II SK (+) (Figure 1).

Figure 1: Sanger-sequencing read from nucleotide 253 to 294 by T3 polymerase. CAA mutation highlighted in yellow with C substituted to A at position 285.

Apart from generating the mutation, I learned how to conduct research on live animals during my work in the fish facility. I bred and cared for zebrafish embryos until up to 5 days post-fertilisation period during which they are not regulated under a Home Office licence. I practiced my microinjection skills into one-cell stage embryos. My fascination only grew stronger and I found myself peaking at the embryos throughout the day to witness the one cell splitting into 4-, 8- and 16-cells forming a plate on top of the yolk and was amazed how, in the span of only 48 hours, I could make out the heart structure and observe the heartbeat under a stereomicroscope. Another interesting aspect of this project was to investigate the H100Q-NRAP mutation in Pinniped and hypothesize its origin in Otariids and Odobenidae.

Overall, I was thrilled to discover how different aspects of biology, from molecular biology, and genetics to developmental biology and physiology came together in this project. It reminded me once again of the importance to follow a big-picture approach and that scientific understanding can seldom follow from isolated observations. The point is, however, to put them into the context of constant change interplay with each other and the environment. A continuation of this project would on the one hand be useful to further aid the scientific understanding of cold adaptations and hibernations to conserve ecosystems and species being threatened by climate change and on the other hand understand the physiological implication of heart mutations in humans.

I would like to thank my supervisor Dr. Claire Russell, Dr. Caroline Pellet-Many, Dr. Steve Allen, and Dr. Denis Larkin for their support, insights, well-stocked freezers full of enzymes, and encouragement throughout the whole process. I am also kindly thanking the British Society for Developmental Biology for granting me this fantastic opportunity and opening the doors to the world of scientific research for me. Thank you!

References

Buggiotti, L.; Yurchenko, A.A.; Yudin, N.S.;  Vander Jagt, C.J.; Vorobieva, N.V.; Kusliy, M. A.; Vasiliev, S.K.; Rodionov, A.N.; Boronetskaya, O.I.; Zinovieva, N.A.; Graphodatsky, A.S.;  Daetwyler, H.D; Larkin, D.M. (2021) ‘Demographic History, Adaptation, and NRAP Convergent Evolution at Amino Acid Residue 100 in the World Northernmost Cattle from Siberia’, Molecular Biology and Evolution, V(38), Issue(8), pp. 3093–3110, https://doi.org/10.1093/molbev/msab078

GeneCards (2022) NRAP gene – Nebulin related anchoring protein. Available at: NRAP Gene – GeneCards | NRAP Protein | NRAP Antibody

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Norwich Single-Cell Symposium 2023

Posted by , on 10 January 2023

Wednesday 3rd May 2023

95.00 GBP

Abstract submission now open!

Now in its sixth year, the Norwich Single-Cell Symposium at Earlham Institute covers single-cell genomics technologies and their application in microbial, plant, animal and human health and disease. Registration is now open!

This event aims to bring together researchers who are curious about applying single cell technologies with those who are experts working at the forefront of the field and across a wide range of species. 

The event will feature talks from keynotes, invited speakers and selected abstracts, and we are keen to capture as broad a range of single-cell applications as possible. Our programme is here.

We’re pleased to confirm our two keynote speakers will be:

Seung Yon (Sue) Rhee, Carnegie Institute for Science

Detlev Arendt, European Molecular Biology Laboratory (EMBL), Heidelberg

We will also be opening up doors to Earlham Institute’s Single-Cell labs, so you will be able to see our technology and capability as well as access our expertise through our researchers.

Registration Deadline: 16 April 2023

Abstract Submission Deadline: 28 February 2023

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Featured Resource: MorphoNet

Posted by , on 10 January 2023

Doing great science depends on teamwork, whether this is within the lab or in collaboration with other labs. However, sometimes the resources that support our work can be overlooked. Our ‘Featured resource’ series aims to shine a light on these unsung heroes of the science world. In our latest article, we hear from Patrick Lemaire and Emmanuel Faure, who describes the work of MorphoNet.

Patrick Lemaire1 and Emmanuel Faure 2

  1. CRBM, Université de Montpellier, CNRS, 34293 Montpellier, France.
  2. LIRMM, Université de Montpellier, CNRS, 34095 Montpellier, France

What is MorphoNet?

MorphoNet (1) is an interactive morphodynamic web browser designed to help scientists, teachers and students share, analyze and visualize the large 3D morphological datasets that can be generated by modern imaging technology, ranging from live light sheet microscopy of cells and embryos to X Ray tomography of fossils.

Why did you build MorphoNet?

We initially created MorphoNet so that our biologist collaborators can interact, without programming skills, with the 3D + time datasets they obtained by light sheet microscopy of live ascidian embryos followed by segmentation (2). We wanted the system to be web-based so that they do not have to install any sophisticated software on their computers, and to allow data sharing. We therefore chose to use a very popular gaming engine Unity, to show meshed segmented data. This choice allowed us to compress the complex 3D + time datasets sufficiently so that they could be explored, curated and shared through an intuitive graphical user interface, running on a standard web browser. In a similar way as genomic browsers display genetic features and epigenetic or gene expression data as traces onto the primary genome sequence, quantitative and qualitative information can be imported and projected onto individual or grouped segmented objects in MorphoNet. These ‘morphological augmentations’ can be saved and shared with other users (and used in publications), respecting the FAIR philosophy.

Can I use the system with my data?

Of course! It’s open-source, publicly available and we commit not to make any scientific use of your private data! After a free registration to the service, you can upload up to 10Gb of data. This space is sufficient for 20 movies like the one shown in Figure 1 – top left. If you need more storage, please contact us, we will find a solution. There are two ways of uploading your own data to MorphoNet: isolated time points can be uploaded with a dedicated Fiji plugin: https://morphonet.org/help_fiji.

More complex datasets (e.g. time series) can be uploaded through the python API: https://morphonet.org/help_api

What type of data can I upload and visualize?

Although users can upload and visualize raw intensity images, MorphoNet’s full potential is unleashed when working with 3D (+ time) segmented data. If you have not yet generated meshes for your segmentations, the system will automatically perform this task for you.

MorphoNet actually offers more flexibility than genome browsers. While the DNA base pair is the universal unit of information in genome browsers, the choice of the relevant morphological unit of information (i.e., the scale of the segmented objects) in MorphoNet is left to the user, from whole organs down to molecular complexes (Figure 1). Like any web-based system MorphoNet has some limitations, which are progressively lifted as the webGL technology is progressing. It is currently difficult to visualize tissues of embryos with more than a couple of thousand segmented cells or objects.

Figure 1: Screen Capture of several datasets available on MorphoNet
– top left :  Astec-Pm1 (Wild type Phallusia mammillata embryo, live SPIM imaging, stages 8-17)
– top middle: Floral Meristem Atlas, stage 0 – 4
– top right: Nest of termites Cubitermes (X-ray tomography)
-middle left: Human body structure (Healthy adult, full-body MRI)
-middle middle: Caenorhabditis elegans (Wild type, adult)
-middle right: Drosophila melanogaster medulla connectome (Wild type, TEM imaging, adult)
-bottom left : Atlas of human brain (Healthy adult, MRI)
-bottom middle: Cascolus ravitis (Fossil, digitally captured images)
-bottom right: Mango tree (Simulated, growth)

Can I see inside the imaged object?

Uploaded datasets are fully interactive. You can rotate, zoom in or out, and click on each individual object. To explore the inside of your segmented structures, you can easily remove entire cell layers, or individually select and hide individual objects. You can also use the scatter view to literally explode all objects radially to clearly visualize each of them (See below).

Can I simultaneously visualise different types of segmented objects (e.g., nuclei within whole cells)?

Yes. You can upload datasets with several segmented channels, obtained from membrane and nuclei recordings, for example. You can also directly add your raw intensity images to your scene. This can be very useful to see gene expression over cell segmentation for example.

Can I annotate my dataset with MorphoNet?

Yes. MorphoNet can be used to add different types of annotations to your dataset: temporal (i.e. to link objects through time), qualitative (for example, to name objects), quantitative (to attribute a value to each individual element, for example cell volume (see below)), a selection value (a given number for each objects) and others (details of the formats used can be found here https://morphonet.org/help_format ). You can either directly label your objects in the scene or upload an annotation file.

Annotating cell volume

Can I assess the quality of my segmentation with the original microscope images?

Yes, you can upload the original microscope images used to segment your dataset and compare them with your segmented data. You can either display the full 3D volume using a threshold value to remove the background or just show some slices in X, Y or Z. You can have a look at this example.

Can I use MorphoNet to visualize Gene Expression Data?

Yes, for ascidian embryos, MorphoNet is interfaced to the gene expression section of the ANISEED database (https://www.aniseed.cnrs.fr) (See Figure 2 and movie below).  Other external gene expression databases could be connected to MorphoNet in the future, and we will be happy to work with you on such projects. If no gene expression database is available for your organism, you can directly upload your expression profiles using a simple format (https://morphonet.org/help_format) and then, as we did with the Arabidopsis meristem (3), you can manually curate, if necessary, your gene expression information by labeling individual cells.

To explore gene expression data, each individual gene can be assigned a colour, and the powerful MorphoNet shaders allow you to simultaneously visualize the expression profiles of up to 4 genes. You can also interrogate your data for genes expressed in the intersection or the union of some specific selected cells.

Figure 2: Screen capture of a multiple gene expression data on an ascidian embryo. The gene expression profiles are extracted from the ANISEED database (https://www.aniseed.cnrs.fr).

Can I explore the cell lineage?

MorphoNet is a unique tool which allows you to interact at the same time with your 3D+t dataset and the corresponding lineage. We use a second window to display the cell lineage and each click on a specific cell will also be displayed on the lineage. You can also map supplementary information, such as the cell volume, on the lineage  and then order the branches by these values.

How can I make nice figures from MorphoNet?

We recently implemented a new module (inside the tools menu), which allows you to create your own figures in pdf format. You can also create your own movies in MorphoNet. Simply define some key frames and MorphoNet will interpolate the rest.

How can I share data with my colleagues?

You can easily share a specific dataset you own with any colleague who registered to MorphoNet. If you want to share multiple datasets, you can group them into a working group, which can be shared.  You can also use MorphoNet to share data publicly, in an article for instance. For this, you can create a session, with a permanent url that can be shared (Just click here as an example https://morphonet.org/hgCbNDIV).

Can I do more if I can code? 

You can directly query your data using the python API : https://morphonet.org/help_api. It is very useful when you have many datasets or when you automatically compute some properties.  We are also developing a Plot module which allows us to directly visualize your data inside our 3D viewer without any data upload.  And you can, of course, contribute! MorphoNet is an open-source software. Please contact us if you are interested. We are having a lot of fun.

What are the next features that you plan to add in MorphoNet?

We have several projects underway. We are currently working on a standalone application which you can directly install on your computer to fully exploit its computational resources when interacting with big datasets.

We are also working on the Virtual Reality representation of your data. This will allow you to interact with your own data with a classical VR headset.

Stay tuned!  You can follow us on Twitter @MorphoTweet

REFERENCES:

  1. B. Leggio, J. Laussu, A. Carlier, C. Godin, P. Lemaire, E. Faure, MorphoNet : an interactive online morphological browser to explore complex multi-scale data. Nat Commun. 10, 1–8 (2019).
  2. L. Guignard, U.-M. Fiúza, B. Leggio, J. Laussu, E. Faure, G. Michelin, K. Biasuz, L. Hufnagel, G. Malandain, C. Godin, P. Lemaire, Contact area–dependent cell communication and the morphological invariance of ascidian embryogenesis. Science. 369, aar5663 (2020).
  3. Refahi et al.    A multiscale analysis of early flower development in Arabidopsis provides an integrated view of molecular regulation and growth control. Developmental Cell, Elsevier, 2021, 56 (4), pp.540-556.e8. ⟨10.1016/j.devcel.2021.01.019⟩
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