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 |
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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 |
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