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

Nature volume 400, pages 69–73 (1999)Cite this article

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.

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Figure 1: Expression of Mox1 and Mox2 in the paraxial mesoderm and the limb buds of mouse embryos.
Figure 2: Targeted disruption of the Mox2 locus.
Figure 3: Limb muscle defects of Mox2− homozygous mutants.
Figure 4: Limb muscle morphogenesis is disrupted in Mox2−/− embryos.
Figure 5: Gene expression in migrating limb myoblasts of Mox2−/− embryos.
Figure 6: Differential expression of MyoD and Myf5 genes in limb myoblasts of Mox2−/− embryos.

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Acknowledgements

We thank S. Tajbakhsh for providing us with the Splotch2H embryos; R. Balling, P.Gruss and K. Jagla for providing us with Pax1, Pax3, and Lbx1 probes, respectively; T. Partridge for expert advice on histopathology; S. Hughes for useful discussions; H. Boyes for animal husbandry; and F.Costantini, in whose laboratory this work was initiated. This work was supported by the MRC.

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Author notes

  1. Peter Ashby

    Present address: Wellcome Trust Building, University of Dundee, WTB/MSI Complex, Dow Street, Dundee, DD1 5EH, UK

  2. Larysa H. Pevny

    Present address: Developmental Genetics Programme, Krebs Institute, University of Sheffield, Sheffield, S10 2NT, UK

  3. Albert Candia

    Present address: Department of Developmental Biology, Stanford University, Stanford, California, 94305, USA

Authors and Affiliations

  1. Divisions of Developmental Neurobiology, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Baljinder S. Mankoo, Nina S. Collins, Elena Grigorieva & Vassilis Pachnis

  2. Divisions of Eukaryotic Molecular Genetics, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Peter Ashby & Peter W. J. Rigby

  3. Divisions of Developmental Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Larysa H. Pevny

  4. Divisions of Vanderbilt Medical School, B2317A MCN, 1161 21st Avenue South, Nashville, 37232-2175, Tennessee, USA

    Albert Candia & Christopher V. E. Wright

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  1. Baljinder S. Mankoo
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Correspondence to Vassilis Pachnis.

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Mankoo, B., Collins, N., Ashby, P. et al. Mox2 is a component of the genetic hierarchy controlling limb muscle development. Nature 400, 69–73 (1999). https://doi.org/10.1038/21892

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