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Mox2 is a component of the genetic hierarchy controlling limb muscle development

Author

Listed:
  • Baljinder S. Mankoo

    (Divisions of Developmental Neurobiology)

  • Nina S. Collins

    (Divisions of Developmental Neurobiology)

  • Peter Ashby

    (Divisions of Eukaryotic Molecular Genetics
    University of Dundee)

  • Elena Grigorieva

    (Divisions of Developmental Neurobiology)

  • Larysa H. Pevny

    (MRC National Institute for Medical Research
    University of Sheffield)

  • Albert Candia

    (Divisions of Vanderbilt Medical School
    Stanford University)

  • Christopher V. E. Wright

    (Divisions of Vanderbilt Medical School)

  • Peter W. J. Rigby

    (Divisions of Eukaryotic Molecular Genetics)

  • Vassilis Pachnis

    (Divisions of Developmental Neurobiology)

Abstract

The skeletal muscles of the limbs develop from myogenic progenitors that originate in the paraxial mesoderm and migrate intothe limb-bud mesenchyme1. 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)2,3,4 and Pax3, a paired-type homeobox gene that is critical for the development of limb musculature5,6,7. Mox1 and Mox2 are closely related homeobox genes that are expressed in overlapping patterns in the paraxial mesoderm and its derivatives8,9. 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.

Suggested Citation

  • Baljinder S. Mankoo & Nina S. Collins & Peter Ashby & Elena Grigorieva & Larysa H. Pevny & Albert Candia & Christopher V. E. Wright & Peter W. J. Rigby & Vassilis Pachnis, 1999. "Mox2 is a component of the genetic hierarchy controlling limb muscle development," Nature, Nature, vol. 400(6739), pages 69-73, July.
    • Handle: RePEc:nat:nature:v:400:y:1999:i:6739:d:10.1038_21892
    DOI: 10.1038/21892
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