title: Cripto regulates skeletal muscle regeneration and modulates satellite cell determination by antagonizing myostatin.
abstract: Skeletal muscle regeneration mainly depends on satellite cells, a population of resident muscle stem cells. However, our understanding of the molecular mechanisms underlying satellite cell activation is still largely undefined. Here, we show that Cripto, a regulator of early embryogenesis, is a novel regulator of muscle regeneration and satellite cell progression toward the myogenic lineage. Conditional inactivation of cripto in adult satellite cells compromises skeletal muscle regeneration, whereas gain of function of Cripto accelerates regeneration, leading to muscle hypertrophy. Moreover, we provide evidence that Cripto modulates myogenic cell determination and promotes proliferation by antagonizing the TGF-β ligand myostatin. Our data provide unique insights into the molecular and cellular basis of Cripto activity in skeletal muscle regeneration and raise previously undescribed implications for stem cell biology and regenerative medicine.
authors.affiliation: Stem Cell Fate Laboratory, Institute of Genetics and Biophysics "Adriano Buzzati-Traverso," Consiglio Nazionale delle Ricerche, 80131 Naples, Italy.
authors.forename: Ombretta
authors.initials: O
authors.lastname: Guardiola
authors.forename: Peggy
authors.initials: P
authors.lastname: Lafuste
authors.forename: Silvia
authors.initials: S
authors.lastname: Brunelli
authors.forename: Salvatore
authors.initials: S
authors.lastname: Iaconis
authors.forename: Thierry
authors.initials: T
authors.lastname: Touvier
authors.forename: Philippos
authors.initials: P
authors.lastname: Mourikis
authors.forename: Katrien
authors.initials: K
authors.lastname: De Bock
authors.forename: Enza
authors.initials: E
authors.lastname: Lonardo
authors.forename: Gennaro
authors.initials: G
authors.lastname: Andolfi
authors.forename: Ann
authors.initials: A
authors.lastname: Bouché
authors.forename: Giovanna L
authors.initials: GL
authors.lastname: Liguori
authors.forename: Michael M
authors.initials: MM
authors.lastname: Shen
authors.forename: Shahragim
authors.initials: S
authors.lastname: Tajbakhsh
authors.forename: Giulio
authors.initials: G
authors.lastname: Cossu
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Gabriella
authors.initials: G
authors.lastname: Minchiotti
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism*; D017353:Gene Deletion; D018390:Gene Targeting; D006984:Hypertrophy; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D032446:Myoblasts / Q000378:metabolism / Q000473:pathology; D055435:Myostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D008562:Membrane Glycoproteins; D055435:Myostatin; D009363:Neoplasm Proteins; C489450:Tdgf1 protein, mouse; D004815:Epidermal Growth Factor