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Local retinoic acid signaling directs emergence of the extraocular muscle functional unit

Glenda Evangelina Comai 1, * Markéta Tesařová 2 Valerie Dupé 3 Muriel Rhinn 4 Pedro Vallecillo-García 5 Fabio da Silva 6 Betty Feret 4 Katherine Exelby 7 Pascal Dollé 4 Leif Carlsson 8 Brian Pryce 9 François Spitz 10 Sigmar Stricker 5 Tomáš Zikmund 2 Jozef Kaiser 2 James Briscoe 7 Andreas Schedl 6 Norbert Ghyselinck 4 Ronen Schweitzer 9 Shahragim Tajbakhsh 1, *
* Corresponding author
1 Cellules Souches et Développement / Stem Cells and Development
2 BUT - Brno University of Technology [Brno]
3 IGDR - Institut de Génétique et Développement de Rennes
4 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
5 Freie Universität Berlin
6 IBV - Institut de Biologie Valrose
7 The Francis Crick Institute [London]
8 Umeå University
9 Shriners Hospital for Children [Portland]
10 Génomique et Epigénomique du Développement des Animaux - Genomics and Epigenomics of Animal Development
Abstract : Coordinated development of muscles, tendons, and their attachment sites ensures emergence of functional musculoskeletal units that are adapted to diverse anatomical demands among different species. How these different tissues are patterned and functionally assembled during embryogenesis is poorly understood. Here, we investigated the morphogenesis of extraocular muscles (EOMs), an evolutionary conserved cranial muscle group that is crucial for the coordinated movement of the eyeballs and for visual acuity. By means of lineage analysis, we redefined the cellular origins of periocular connective tissues interacting with the EOMs, which do not arise exclusively from neural crest mesenchyme as previously thought. Using 3D imaging approaches, we established an integrative blueprint for the EOM functional unit. By doing so, we identified a developmental time window in which individual EOMs emerge from a unique muscle anlage and establish insertions in the sclera, which sets these muscles apart from classical muscle-to-bone type of insertions. Further, we demonstrate that the eyeballs are a source of diffusible all-trans retinoic acid (ATRA) that allow their targeting by the EOMs in a temporal and dose-dependent manner. Using genetically modified mice and inhibitor treatments, we find that endogenous local variations in the concentration of retinoids contribute to the establishment of tendon condensations and attachment sites that precede the initiation of muscle patterning. Collectively, our results highlight how global and site-specific programs are deployed for the assembly of muscle functional units with precise definition of muscle shapes and topographical wiring of their tendon attachments.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03027360
Contributor : Glenda Comai <>
Submitted on : Wednesday, December 2, 2020 - 8:47:22 AM
Last modification on : Monday, February 1, 2021 - 4:46:04 PM
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PASTEUR | IGBMC | IGDR | UNIV-RENNES1 | BIOSIT | UR1-UFR-SVE | UNICE | UNIV-COTEDAZUR | UNIV-RENNES | CNRS | SITE-ALSACE | INSERM

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Glenda Evangelina Comai, Markéta Tesařová, Valerie Dupé, Muriel Rhinn, Pedro Vallecillo-García, et al.. Local retinoic acid signaling directs emergence of the extraocular muscle functional unit. PLoS Biology, Public Library of Science, 2020, 18 (11), pp.e3000902. ⟨10.1371/journal.pbio.3000902⟩. ⟨pasteur-03027360⟩

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