Sema3a-Nrp1 Signaling Mediates Fast-Twitch Myofiber Specificity of Tw2

Autor: Rhonda Bassel-Duby, Dileep Karri, Efrain Sanchez-Ortiz, Ning Liu, Eric N. Olson, Stephen Li, Priscilla Jaichander
Rok vydání: 2019
Předmět:
Genetically modified mouse
Male
Satellite Cells
Skeletal Muscle

Cell
Population
Mice
Transgenic

Biology
Ligands
General Biochemistry
Genetics and Molecular Biology

Article
Cell Line
03 medical and health sciences
Mice
0302 clinical medicine
Cell surface receptor
Cell Movement
Chlorocebus aethiops
medicine
Myocyte
Animals
Progenitor cell
Receptor
education
Muscle
Skeletal

Molecular Biology
Transcription factor
Cells
Cultured

030304 developmental biology
Cell Proliferation
0303 health sciences
education.field_of_study
Sequence Analysis
RNA

Stem Cells
Cell Membrane
PAX7 Transcription Factor
Cell Differentiation
Semaphorin-3A
Cell Biology
Neuropilin-1
Cell biology
medicine.anatomical_structure
Gene Expression Regulation
COS Cells
Female
030217 neurology & neurosurgery
Gene Deletion
Developmental Biology
Signal Transduction
Zdroj: Dev Cell
ISSN: 1878-1551
Popis: 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.
Databáze: OpenAIRE