Notch regulation of myogenic versus endothelial fates of cells that migrate from the somite to the limb

• DOI: 10.1073/pnas.1407606111
• Publication Date: 2014-06-04T03:26:28Z
• Authors: Alicia Mayeuf-Lou...; Mounia Lagha; Anne Danckaert; Didier Rocancourt; Frederic Relaix; Stéphane D. Vincent; Margaret Buckingham
• Keywords: Male; 0301 basic medicine; Genetic Vectors; Mice, Transgenic; [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics; [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology; Muscle Development; Mice; 03 medical and health sciences; Cell Movement; Animals; Paired Box Transcription Factors; Cell Lineage; Muscle, Skeletal; PAX3 Transcription Factor; Alleles; Receptors, Notch; [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis; Endothelial Cells; Gene Expression Regulation, Developmental; [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology; Cell Differentiation; Extremities; Forkhead Transcription Factors; [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics; [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis; Female; Signal Transduction

Significance

During embryonic development, multipotent stem cells progressively acquire specific cell fates. The somite is an embryological structure that gives rise to different mesodermal cell types, including skeletal muscle and vascular cells of blood vessels. We show by genetic manipulation that the Notch signaling pathway promotes a vascular cell-fate choice at the expense of skeletal muscle in the mouse somite. Pax3 + cells in the adjacent somites give rise to myogenic and endothelial cells in the limbs. Gain-of-function or inhibition of Notch signaling affects this cell-fate choice prior to the migration of these somite-derived cells into the limb. This embryological role of Notch is of potential therapeutic relevance to deriving stem cells for tissue repair.