Open AccessFhl2 Interacts with Foxk1 and Corepresses Foxo4 Activity in Myogenic Progenitors
Author(s) -
Shi Xiaozhong,
Bowlin Kathy M.,
Garry Daniel J.
Publication year - 2010
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.274
Subject(s) - biology , microbiology and biotechnology , progenitor cell , progenitor , stem cell , cancer research , computational biology
Adult skeletal muscle has a remarkable regenerative capacity because of a myogenic progenitor cell population. Using a gene disruption strategy, we determined that Foxk1 regulates myogenic progenitor cell activation and muscle regeneration. In this study, we undertook a yeast two hybrid screen to identify Foxk1 interacting proteins. We identified the LIM‐only protein, Fhl2, as a Foxk1 interacting protein. Using transcriptional assays, we observed that Fhl2, in a dose‐dependent fashion, promotes Foxk1 transcriptional repression of Foxo4 activity. Using histochemical and immunohistochemical assays, we further established that Fhl2 is expressed in the myogenic progenitor cell population. Fhl2 knockdown results in cell cycle arrest, and mice lacking Fhl2 have perturbed skeletal muscle regeneration. Collectively, these studies define a Fhl2‐Foxk1 cascade that regulates the myogenic progenitor cell activity in adult skeletal muscle and enhances our understanding of muscle regeneration. S TEM C ELLS 2010;28:462–469