Publication detail

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

COMAI, G. TESAŘOVÁ, M. DUPÉ, V. RHINN, M. VALLECILLO-GARCÍA, P. DA SILVA, F. FERET, B. EXELBY, K. DOLLE, P. CARLSSON, L. PRYCE, B. SPITZ, F. STRICKER, S. ZIKMUND, T. KAISER, J. BRISCOE, J. SCHEDL, A. GHYSELINCK, N. SCHWEITZER, R. TAJBAKHSH, S.

Original Title

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

Type

journal article in Web of Science

Language

English

Original 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.

Keywords

eye, extraocular muscles, EOM, embryogenesis, development

Authors

COMAI, G.; TESAŘOVÁ, M.; DUPÉ, V.; RHINN, M.; VALLECILLO-GARCÍA, P.; DA SILVA, F.; FERET, B.; EXELBY, K.; DOLLE, P.; CARLSSON, L.; PRYCE, B.; SPITZ, F.; STRICKER, S.; ZIKMUND, T.; KAISER, J.; BRISCOE, J.; SCHEDL, A.; GHYSELINCK, N.; SCHWEITZER, R.; TAJBAKHSH, S.

Released

17. 11. 2020

Publisher

PLOS

ISBN

1544-9173

Periodical

PLOS BIOLOGY

Year of study

18

Number

11

State

United States of America

Pages from

1

Pages to

33

Pages count

33

URL

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000902

Full text in the Digital Library

http://hdl.handle.net/11012/195766

BibTex

@article{BUT166299,
  author="Glenda {Comai} and Markéta {Kaiser} and Valérie {Dupé} and Muriel {Rhinn} and Pedro {Vallecillo-García} and Fabio {da Silva} and Betty {Feret} and Katherine {Exelby} and Pascal {Dolle} and Leif {Carlsson} and Brian {Pryce} and Francois {Spitz} and Sigmar {Stricker} and Tomáš {Zikmund} and Jozef {Kaiser} and James {Briscoe} and Andreas {Schedl} and Norbert {Ghyselinck} and Ronen {Schweitzer} and Shahragim {Tajbakhsh}",
  title="Local retinoic acid signaling directs emergence of the extraocular muscle functional unit",
  journal="PLOS BIOLOGY",
  year="2020",
  volume="18",
  number="11",
  pages="1--33",
  doi="10.1371/journal.pbio.3000902",
  issn="1544-9173",
  url="https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000902"
}