Mox2 is a component of the genetic hierarchy controlling limb muscle development.
The skeletal muscles of the limbs develop from myogenic progenitors that originate in the paraxial mesoderm and migrate into the limb-bud mesenchyme. Among the genes known to be important for muscle development in mammalian embryos are those encoding the basic helix-loop-helix (bHLH) myogenic regulatory factors (MRFs; MyoD, Myf5, myogenin and MRF4) and Pax3, a paired-type homeobox gene that is critical for the development of limb musculature. Mox1 and Mox2 are closely related homeobox genes that are expressed in overlapping patterns in the paraxial mesoderm and its derivatives. Here we show that mice homozygous for a null mutation of Mox2 have a developmental defect of the limb musculature, characterized by an overall reduction in muscle mass and elimination of specific muscles. Mox2 is not needed for the migration of myogenic precursors into the limb bud, but it is essential for normal appendicular muscle formation and for the normal regulation of myogenic genes, as demonstrated by the downregulation of Pax3 and Myf5 but not MyoD in Mox2-deficient limb buds. Our findings show that the MOX2 homeoprotein is an important regulator of vertebrate limb myogenesis.
Division of Developmental Neurobiology, MRC National Institute for Medical Research, London, UK.
B S
BS
Mankoo
N S
NS
Collins
P
P
Ashby
E
E
Grigorieva
L H
LH
Pevny
A
A
Candia
C V
CV
Wright
P W
PW
Rigby
V
V
Pachnis
D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface / Q000235:genetics* / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology; D005121:Extremities / Q000196:embryology*; D015870:Gene Expression; D018390:Gene Targeting; D005801:Genes, Homeobox; D017930:Genes, Reporter; D008297:Male; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D018482:Muscle, Skeletal / Q000002:abnormalities / Q000196:embryology*; D009154:Mutation; D018008:Myogenin / Q000235:genetics
D015703:Antigens, CD; D000954:Antigens, Surface; C503801:Myog protein, mouse; D018008:Myogenin; C042739:antigens, CD200