Loss of myogenin in postnatal life leads to normal skeletal muscle but reduced body size.
Although the mechanisms regulating the formation of embryonic skeletal muscle in vertebrates are well characterized, less is known about postnatal muscle formation even though the largest increases in skeletal muscle mass occur after birth. Adult muscle stem cells (satellite cells) appear to recapitulate the events that occur in embryonic myoblasts. In particular, the myogenic basic helix-loop-helix factors, which have crucial functions in embryonic muscle development, are assumed to have similar roles in postnatal muscle formation. Here, we test this assumption by determining the role of the myogenic regulator myogenin in postnatal life. Because Myog-null mice die at birth, we generated mice with floxed alleles of Myog and mated them to transgenic mice expressing Cre recombinase to delete Myog before and after embryonic muscle development. Removing myogenin before embryonic muscle development resulted in myofiber deficiencies identical to those observed in Myog-null mice. However, mice in which Myog was deleted following embryonic muscle development had normal skeletal muscle, except for modest alterations in the levels of transcripts encoding Mrf4 (Myf6) and Myod1 (MyoD). Notably, Myog-deleted mice were 30% smaller than control mice, suggesting that the absence of myogenin disrupted general body growth. Our results suggest that postnatal skeletal muscle growth is controlled by mechanisms distinct from those occurring in embryonic muscle development and uncover an unsuspected non-cell autonomous role for myogenin in the regulation of tissue growth.
Knapp
Jennifer R
JR
Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Davie
Judith K
JK
Myer
Anita
A
Meadows
Eric
E
Olson
Eric N
EN
Klein
William H
WH
D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D049628:Body Size; D020964:Embryo Loss; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism*
D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018006:Myogenic Regulatory Factors; D018008:Myogenin; C063403:myogenic factor 6