Absence of p21CIP rescues myogenic progenitor cell proliferative and regenerative capacity in Foxk1 null mice

Thomas J. Hawke, Nan Jiang, Daniel J. Garry

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Foxk1 is a forkhead/winged helix transcription factor that is restricted to myogenic progenitor cells in adult skeletal muscle. Mice lacking Foxk1 (Foxk1-/-) display growth retardation and a severe impairment in skeletal muscle regeneration following injury. Here we show that myogenic progenitor cells from Foxk1-/- mice are reduced in number and have perturbed cell cycle progression (G0/G1 arrest). Molecular analysis of Foxk1-/- myogenic progenitor cells revealed increased expression of the cyclin-dependent kinase inhibitor, p21CIP, independent of changes in other cell cycle inhibitors, including p53. Combinatorial mating of Foxkl-/- mice with p21CIP-/- mice, to generate double mutant progeny, resulted in a complete restoration of the growth deficit, skeletal muscle regeneration, myogenic progenitor cell number, and cell cycle progression that characterized the Foxk1-/- mice. We conclude that Foxk1 is essential for regulating cell cycle progression in the myogenic progenitor cell and that the cyclin-dependent kinase inhibitor, p21CIP, may be a downstream target of Foxk1.

Original languageEnglish (US)
Pages (from-to)4015-4020
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number6
DOIs
StatePublished - Feb 7 2003

Fingerprint

Dive into the research topics of 'Absence of p21<sup>CIP</sup> rescues myogenic progenitor cell proliferative and regenerative capacity in Foxk1 null mice'. Together they form a unique fingerprint.

Cite this