Hoxa2 plays a direct role in murine palate development.
The cleft palate exhibited by Hoxa2 null murine embryos has been described as being secondary to abnormalities of tongue musculature, and Hoxa2 was presumed to not play a direct role in palate development. However, we detected Hoxa2 expression in the developing palate at both the mRNA and protein levels between embryonic day (E) 12.5 and E15.5. Organ cultures of Hoxa2(-/-) palates maintained in the absence of the tongue showed decreased fusion rates than either Hoxa2(+/-) or Hoxa2(+/+) palate cultures. Knocking down Hoxa2 expression with antisense retroviral constructs resulted in decreased fusion rates than corresponding controls. An overall increase in cell proliferation was observed in Hoxa2 null palates providing a potential mechanism by which Hoxa2 may be affecting palate development. Hoxa2 also repressed the expression of its downstream targets Msx1, Bmp4, Barx1, and Ptx1 within the palate. These results demonstrate the cleft palate phenotype of Hoxa2 null embryos is not solely due to abnormal tongue musculature, and indicate a direct role of Hoxa2 in regulating murine palatogenesis.
Smith
Tara M
TM
Laboratory of Molecular Biology, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Wang
Xia
X
Zhang
Wei
W
Kulyk
William
W
Nazarali
Adil J
AJ
D000818:Animals; D015153:Blotting, Western; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D049109:Cell Proliferation; D002972:Cleft Palate / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051957:MSX1 Transcription Factor / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009924:Organ Culture Techniques; D051761:Paired Box Transcription Factors / Q000378:metabolism; D010159:Palate / Q000196:embryology* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism
C095587:Barx1 protein, mouse; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D018398:Homeodomain Proteins; C489833:Hoxa2 protein, mouse; D051957:MSX1 Transcription Factor; C484084:Msx1 protein, mouse; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C101485:homeobox protein PITX1