Transcriptional control of chordate morphogenesis

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We study the embryos of ascidians, a group of small marine invertebrates some of which are seen as delicacies in France and Japan (sea squirts, sea pineapples). We chose this group of animals because the different species included in this group have very different genomes, but develop in an almost identical manner, such that homologous cells can be found across all embryos of a species, and even between distantly related species!

To understand this apparent paradox, we combine light-sheet imaging of live embryos, (epi)genome sequencing, classical embryology and computer modelling. Our hope is that this work will allow us to better understand the sometimes tortuous paths of species evolution.

Biologists have long been puzzled by the different rates of morphological evolution of animal species. Why do some taxa undergo rapid morphological changes while others, such as the coelacanth, can keep very similar morphologies over hundreds of millions of years? Is this correlated with the rates of genome divergence, or does this involve specific mechanisms to buffer or enhance the impact of genetic divergence? Our group is exploring the complex relationships between genotype and phenotype at the crossroad of developmental biology, computational biology, evolutionary biology and cell biology.

As a model system we use the embryos of ascidians (Left) because of the anatomical and genomic simplicity of these marine invertebrates, which are closely related to vertebrates. These embryos develop with a fixed cell lineage that is remarkably well conserved between all studied species, even in those with genomes that have extensively diverged for up to 400 million years of parallel evolution. Ascidians thus offer a unique opportunity to decipher the developmental program of a chordate with a cellular level of resolution, and to understand how genomic plasticity is compatible with morphological conservation. This latter phenomenon is referred to as Developmental Systems Divergence (DSD) and may explain why the modelling of human diseases in animal models is not always successful.

To identify the molecular and cellular mechanisms underlying the striking evolutionary stability of ascidian morphogenesis, we combine advanced quantitative imaging with epigenetics, transcriptomics and cis-regulatory analyses. Our major aims are: 1) to elucidate the evolution of the repertoire of developmental ascidian regulatory proteins and their regulation; 2) to fully reconstruct and quantify the single-cell dynamics and cell lineage trees during ascidian morphogenesis and its evolution through advanced light-sheet microscopy and computational image analysis.

Have a look at the small animation movie made by Laurence Serfaty and Isis Leterrier, two professional directors, about our work on the computational reconstruction of embryogenesis with single cell resolution, and how the range of cell communication may play a role in the cellular reproducibility of development.

Contact our team

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Patrick Lemaire

Members of the team

  • Mathieu BONREPAUX
    (Research Assistant) +33 (0)4 34 35 95 59
  • Jean-Philippe CHAMBON
    (Staff Scientist) +33 (0)4 34 35 95 59
  • Christelle DANTEC
    (Research Assistant) +33 (0)4 34 35 95 59
  • Patrick LEMAIRE Group Leader
    (Staff Scientist) NULL
  • Ingrid MORMIN
    (Research Assistant) +33 (0)4 34 35 95 46
  • Jacques PIETTE
    (Staff Scientist) +33 (0)4 34 35 95 63
  • Lisa THOMANN
    (PhD Student) +33 (0)4 34 35 9
    • 2020
    • 2020

      Contact Area-Dependent Cell Communication and the Morphological Invariance of Ascidian Embryogenesis

      Léo Guignard, Ulla-Maj Fiúza, Bruno Leggio , Julien Laussu, Emmanuel Faure, Gaël Michelin, Kilian Biasuz, Lars Hufnagel, Grégoire Malandain, Christophe[...]

      Science . 369(6500):eaar5663. Pubmed

    • 2020

      Contact-area dependent cell communications and the morphological invariance of ascidian embryogenesis

      Guignard L*, Fiuza UM*, Leggio B, Laussu J, Faure E, Michelin G, Biasuz K, Hufnagel L, Malandain G#, Godin G#,[...]

      In press Pubmed

    • 2020

      Nodal and Eph signalling relay drives the transition between apical constriction and apico-basal shortening during ascidian endoderm invagination

      Fiuza UM, Negishi T, Rouan A, Yasuo H# and Lemaire P#

      Development Pubmed

    • 2020

      ANISEED 2019: 4D exploration of genetic data for an extended range of tunicates

      Dardaillon J, Dauga D, Simion P, Faure E, Onuma TA, DeBiasse MB, Louis A, Nitta KR, Naville M, Besnardeau L,[...]

      Nucleic Acids Res. gkz955 Pubmed

    • 20192019

      Evolution of the embryonic cis-regulatory landscapes between divergent Phallusia and Ciona ascidians

      Madgwick , Magri MS, Dantec C, Gailly D, Fiuza UM, Guignard L, Hettinger S, Gomez-Skarmeta JL, and Lemaire P

      Dev Biol. 448(2):71-87 Pubmed

    • 20192019

      High-Throughput Protein Production Combined with High-Throughput SELEX Identifies an Extensive Atlas of Ciona robusta Transcription Factor DNA-Binding Specificities

      Nitta KR, Vincentelli R, Jacox E, Cimino A, Ohtsuka Y, Sobral D, Satou Y, Cambillau C, and Lemaire P

      Methods Mol Biol. 2025:487-517 Pubmed

    • 20192019

      MorphoNet: An interactive online morphological browser to explore complex multi-scale data

      Leggio B, Laussu J, Carlier A, Godin C, Lemaire P and Faure E

      Nat. Commun. 10(1):2812 Pubmed

    • 2019

      Multiscale mechanical model for cell division orientation in developing biological systems

      Leggio B, Laussu J, Faure E, Lemaire P and Godin C

      bioRxiv 785337 Pubmed

    • 2018

      ANISEED 2017: extending the integrated ascidian database to the exploration and evolutionary comparison of genome-scale datasets.

      Brozovic M, Dantec C, Dardaillon J, Dauga D, Faure E, Gineste M, Louis A, Naville M, Nitta KR, Piette J,[...]

      Nucleic Acids Res. 46(D1):D718-D725. Pubmed

    • 2018

      ANISEED 2017: extending the integrated ascidian database to the exploration and evolutionary comparison of genome-scale datasets.

      Brozovic M, Dantec C, Dardaillon J, Dauga D, Faure E, Gineste M, Louis A, Naville M, Nitta KR, Piette J,[...]

      Nucleic Acids Res. 46(D1):D718-D725. Pubmed

    • 2018

      A phylogenomic framework and timescale for comparative studies of tunicates.

      Delsuc F, Philippe H, Tsagkogeorga G, Simion P, Tilak MK, Turon X, López-Legentil S, Piette J, Lemaire P, Douzery EJP.

      BMC Biol. 16(1):39. Pubmed

    • 2018

      Convergent Acquisition of Nonembryonic Development in Styelid Ascidians.

      Alié A, Hiebert LS, Simion P, Scelzo M, Prünster MM, Lotito S, Delsuc F, Douzery EJP, Dantec C, Lemaire P,[...]

      Mol Biol Evol. 35(7):1728-1743. Pubmed

    • 2017

      Genome-wide survey of miRNAs and their evolutionary history in the ascidian, Halocynthia roretzi.

      Wang K, Dantec C, Lemaire P, Onuma TA, Nishida H.

      BMC Genomics. 18(1):314. Pubmed

    • 2016

      ANISEED 2015: a digital framework for the comparative developmental biology of ascidians.

      Brozovic M, Martin C, Dantec C, Dauga D, Mendez M, Simion P, Percher M, Laporte B, Scornavacca C, Di Gregorio[...]

      Nucleic Acids Res. 44:D808-18. Pubmed

    • 2015

      Guidelines for the nomenclature of genetic elements in tunicate genomes.

      Stolfi A, Sasakura Y, Chalopin D, Satou Y, Christiaen L, Dantec C, Endo T, Naville M, Nishida H, Swalla BJ,[...]

      Genesis. 53:1-14. Pubmed

    • 2015

      Thaliaceans, the neglected pelagic relatives of ascidians : a developmental and evolutionary enigma.

      Piette J, Lemaire P.

      Q Rev Biol. 90:117-45. Pubmed

    • 2015

      Tunicates: exploring the sea shores and roaming the open ocean. A tribute to Thomas Huxley.

      Lemaire P, Piette J.

      Open Biol. 5:150053. Pubmed

    • 2014

      An otx/nodal regulatory signature for posterior neural development in ascidians.

      Roure A, Lemaire P, Darras S.

      PLoS Genet. 10:e1004548. Pubmed

    • 2015

      Guidelines for the nomenclature of genetic elements in tunicate genomes.

      Stolfi A, Sasakura Y, Chalopin D, Satou Y, Christiaen L, Dantec C, Endo T, Naville M, Nishida H, Swalla BJ,[...]

      Genesis. 53(1):1-14. Pubmed

    • 2015

      A pipeline for the systematic identification of non-redundant full-ORF cDNAs for polymorphic and evolutionary divergent genomes: Application to the ascidian Ciona intestinalis.

      Gilchrist MJ, Sobral D, Khoueiry P, Daian F, Laporte B, Patrushev I, Matsumoto J, Dewar K, Hastings KE, Satou Y,[...]

      Dev Biol. 404(2):149-63. Pubmed

    • 2013

      DNA-binding specificities of human transcription factors.

      Jolma A, Yan J, Whitington T, Toivonen J, Nitta KR, Rastas P, Morgunova E, Enge M, Taipale M, Wei G,[...]

      Cell. 152(1-2):327-39. Pubmed

    • 2013

      Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development.

      Sanges R, Hadzhiev Y, Gueroult-Bellone M, Roure A, Ferg M, Meola N, Amore G, Basu S, Brown ER, De Simone[...]

      Nucleic Acids Res. 41(6):3600-18. Pubmed

    • 2012

      Antagonizing retinoic acid and FGF/MAPK pathways control posterior body patterning in the invertebrate chordate Ciona intestinalis.

      Pasini A, Manenti R, Rothbächer U, Lemaire P.

      PLoS One. 7(9):e46193. Pubmed

    • 2011

      Evolutionary crossroads in developmental biology: the tunicates.

      Lemaire P.

      Development. 138(11):2143-52. Pubmed

    • 2011

      Time-lapse imaging of live Phallusia embryos for creating 3D digital replicas.

      Robin FB, Dauga D, Tassy O, Sobral D, Daian F, Lemaire P.

      Cold Spring Harb Protoc. 2011(10):1244-6. Pubmed

    • 2011

      Imaging of fixed ciona embryos for creating 3D digital replicas.

      Robin FB, Dauga D, Tassy O, Sobral D, Daian F, Lemaire P.

      Cold Spring Harb Protoc. 2011(10):1247-50. Pubmed

    • 2011

      Creating 3D digital replicas of ascidian embryos from stacks of confocal images.

      Robin FB, Dauga D, Tassy O, Sobral D, Daian F, Lemaire P.

      Cold Spring Harb Protoc. 2011(10):1251-61. Pubmed

    CONTEXT OF OUR WORK: Developmental Systems Drift

    Biologists have long been puzzled by the different rates of morphological evolution of animal species. Why do some taxa undergo rapid morphological changes while others, such as the coelacanth, can maintain almost the same morphology over hundreds of millions of years? Is this correlated with the rate of genome divergence, or does this involve specific mechanisms to buffer or enhance the effect of genetic divergence? Our group investigates the complex relationships between genotype and phenotype at the crossroad of developmental biology, computational biology, evolutionary biology and cell biology.

    As a model system we use ascidian embryos because of the anatomical and genomic simplicity of these marine invertebrates that are closely related to vertebrates (Left). These embryos develop with fixed cell lineages that are remarkably well conserved in all studied species, even in those with genomes that have extensively diverged during 500 million years of parallel evolution. Therefore, ascidians offer a unique opportunity to decipher a chordate developmental programme with a cellular level of resolution, and to understand how genomic plasticity is compatible with morphological conservation. This latter phenomenon is referred to as Developmental Systems Divergence (DSD) and may explain why human disease modelling in animal models is not always successful.

    To identify the molecular and cellular mechanisms underlying the striking evolutionary stability of ascidian morphogenesis, we combine advanced quantitative imaging using light-sheet microscopy with epigenetic, transcriptomic and cis-regulatory analyses. Our main research aims are: 1) to elucidate the evolution of the repertoire and function of proteins that regulate ascidian development; 2) to quantify ascidian morphogenesis and its evolution by using advanced light-sheet microscopy and computational image analysis, 3) ultimately, to computationally simulate developmental dynamics.

    SOFTWARE and DATABASES:

    ANISEED: the tunicate model organism database

    ASTEC: Automated Segmentation and Tracking of Embryonic cells.

    MorphoNet : an interactive online morphological browser to explore complex multi-scale imaging data