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MYOPTAH

Muscle architecture plans in the embryo
Funder: French National Research Agency (ANR)Project code: ANR-24-CE13-2114
Funder Contribution: 681,610 EUR
Description

While early morphogenesis of skeletal muscles has been extensively studied in amniotes, many basic questions on later events of muscle patterning are still unknown. Based on exciting preliminary data collected by the Maire and Marcelle teams, we propose to use the chicken and the mouse models to decipher the role of so-called "primary and secondary myotubes" in the building of functional skeletal muscles. Anatomists studying muscle formation in vertebrate embryos half a century ago have identified two distinct waves of myogenesis. The first, taking place during the embryonic phase of development, generates primary myotubes. The second, observed in fetal life, results in the emergence of secondary myotubes. It is suspected that primary myotubes serve as scaffolds for the morphogenesis of the secondary lineage. Primary myotubes form before motoneurons reach the muscle masses. Myoblasts present in muscle masses during the emergence of primary and secondary myotubes (named embryonic and fetal myoblasts, respectively) display distinct morphological and biochemical characteristics in vitro. By addressing the embryonic origin and functional importance of primary and secondary myogenesis, our multi-level, multi-species project will result in key advances in our understanding of the cellular and molecular mechanisms regulating late events of myogenesis and that a comprehensive model describing muscle formation from the earliest signs of its incipience to late events of fiber type patterning will emerge from this study. We will use state of the art approaches including mouse genetic models, lineage tracing in the mouse embryo, recently developed snRNA-seq approaches, live high resolution imaging in the chick embryo to tackle the origin of myogenic progenitors’ diversity and their role in building the neuromuscular system. We will further characterize how primary myogenesis instruct secondary myogenesis and later muscle growth.

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