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Publication : Sema3a-Nrp1 Signaling Mediates Fast-Twitch Myofiber Specificity of Tw2<sup>+</sup> Cells.

First Author  Li S Year  2019
Journal  Dev Cell Volume  51
Issue  1 Pages  89-98.e4
PubMed ID  31474563 Mgi Jnum  J:281761
Mgi Id  MGI:6380749 Doi  10.1016/j.devcel.2019.08.002
Citation  Li S, et al. (2019) Sema3a-Nrp1 Signaling Mediates Fast-Twitch Myofiber Specificity of Tw2(+) Cells. Dev Cell 51(1):89-98.e4
abstractText  We previously identified a unique population of interstitial muscle progenitors, marked by expression of the Twist2 transcription factor, which fuses specifically to type IIb/x fast-twitch myofibers. Tw2(+) progenitors are distinct from satellite cells, a muscle progenitor that expresses Pax7 and contributes to all myofiber types. Through RNA sequencing and immunofluorescence, we identify the membrane receptor, Nrp1, as a marker of Tw2(+) cells but not Pax7(+) cells. We also found that Sema3a, a chemorepellent ligand for Nrp1, is expressed by type I and IIa myofibers but not IIb myofibers. Using stripe migration assays, chimeric cell-cell fusion assays, and a Sema3a transgenic mouse model, we identify Sema3a-Nrp1 signaling as a major mechanism for Tw2(+) cell fiber-type specificity. Our findings reveal an extracellular signaling mechanism whereby a cell-surface receptor for a chemorepellent confers specificity of intercellular fusion of a specific muscle progenitor with its target tissue.
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