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Vol. 13, No. 24, pp. 3231-3243, December 15, 1999
1 Department of Genetics and 2 Department of
Biochemistry and Molecular Biology, Harvard Medical School, Boston,
Massachusetts 02115 USA; 3 Department of Pathology, Baylor
College of Medicine, Houston, Texas 77030 USA; 4 Department of
Genetics, St. Jude's Children's Research Hospital, Memphis, Tennessee
38105 USA; 5 National Eye Institute, National Institutes of
Health (NIH), Bethesda, Maryland 20892 USA
We have identified a novel vertebrate homolog of the
Drosophila gene dachshund, Dachshund2
(Dach2). Dach2 is expressed in the developing somite
prior to any myogenic genes with an expression profile similar to
Pax3, a gene previously shown to induce muscle differentiation.
Pax3 and Dach2 participate in a positive regulatory feedback loop, analogous to a feedback loop that exists in
Drosophila between the Pax gene eyeless (a
Pax6 homolog) and the Drosophila dachshund gene.
Although Dach2 alone is unable to induce myogenesis, Dach2 can synergize with Eya2 (a vertebrate homolog of
the Drosophila gene eyes absent) to regulate myogenic
differentiation. Moreover, Eya2 can also synergize with
Six1 (a vertebrate homolog of the Drosophila gene
sine oculis) to regulate myogenesis. This synergistic regulation of muscle development by Dach2 with Eya2 and
Eya2 with Six1 parallels the synergistic regulation of
Drosophila eye formation by dachshund with eyes
absent and eyes absent with sine oculis. This
synergistic regulation is explained by direct physical interactions between Dach2 and Eya2, and Eya2 and Six1 proteins, analogous to
interactions observed between the Drosophila proteins. This study reveals a new layer of regulation in the process of myogenic specification in the somites. Moreover, we show that the Pax, Dach, Eya, and Six genetic network has been
conserved across species. However, this genetic network has been used
in a novel developmental context, myogenesis rather than eye
development, and has been expanded to include gene family members that
are not directly homologous, for example Pax3 instead of
Pax6.
[Key Words: Dach2; Eya2; Six1; Pax3; myogenesis; dachshund; somite development]
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