Mouse Dach1 and Dach2 are redundantly required for Müllerian duct development.
dachshund/Dach gene family members encode transcriptional cofactors with highly conserved protein interaction domains and are expressed in the developing eyes, brains, and limbs in insects and vertebrates. These observations suggest that the developmental roles of dachshund/Dach in these tissues have been conserved since the divergence of arthropods and chordates. However, while Drosophila dachshund mutants have abnormalities in eye, brain, limbs, mouse Dach1 or Dach2 knockout mutants do not exhibit gross anatomical malformations in these tissues. In addition, Dach1/2 double homozygotes have intact eyes and limbs. Here we show that in Dach1/Dach2 double mutants, female reproductive tract (FRT) development is severely disrupted. This defect is associated with the Müllerian duct (MD) and not the Wolffian duct (WD), which normally differentiate into either the FRT or male reproductive tract (MRT), respectively. Dach1 and Dach2 are expressed in the MD, and in Dach1/2 double mutants, MD expression of Lim1 and Wnt7a is abnormal and MD development is disrupted. In contrast, WD and MRT development are not grossly affected. We propose that Dach1 and Dach2 proteins may redundantly control FRT formation by regulating the expression of target genes required for development of the MD. This vertebrate Dach1/2 function may have been conserved during arthropod evolution, as Drosophila dachshund mutants also exhibit an FRT phenotype.
Davis
Richard J
RJ
Department of Ophthalmology, Columbia University Medical Center, Harkness Eye Institute, New York City, New York.
Harding
Mark
M
Moayedi
Yalda
Y
Mardon
Graeme
G
D000818:Animals; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000502:physiology; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009095:Mullerian Ducts / Q000196:embryology* / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D014928:Wolffian Ducts / Q000196:embryology / Q000502:physiology
D004268:DNA-Binding Proteins; C456264:Dach1 protein, mouse; C485735:Dach2 protein, mouse; D005136:Eye Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors