[PDF][PDF] Sema3a-Nrp1 signaling mediates fast-twitch myofiber specificity of Tw2+ cells

S Li, D Karri, E Sanchez-Ortiz, P Jaichander… - Developmental cell, 2019 - cell.com
S Li, D Karri, E Sanchez-Ortiz, P Jaichander, R Bassel-Duby, N Liu, EN Olson
Developmental cell, 2019cell.com
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 …
Summary
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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