title: Dlx5- and Dlx6-mediated chondrogenesis: Differential domain requirements for a conserved function.
abstract: During endochondral ossification in the vertebrate limb, multipotent mesenchymal cells first differentiate into chondroblasts (chondrogenesis) that further differentiate (via chondrocyte hypertrophy) to a terminal cellular phenotype. Dlx5 and Dlx6 are functionally redundant regulators of chondrocyte hypertrophy. We now show that Dlx5 and Dlx6 also regulate the earlier step of chondrogenesis in the limb. Limb bud mesenchymal cells from Dlx5/6(-/-) embryos show reduced chondrogenesis compared to wild-type littermates, and expression of either Dlx5 or Dlx6 stimulated differentiation of limb bud mesenchymal cells to chondroblasts. The functional overlap between Dlx5 and Dlx6 occurs despite the fact that the amino- and carboxyl-terminal domains of the encoded proteins are dissimilar. In order to reconcile the disparity between the divergent structures of Dlx5 and Dlx6 with their overlapping biological functions, we investigated the domain requirements and transcriptional activities associated with Dlx5- and Dlx6-mediated chondrogenesis. We find distinct domain requirements for the chondrogenic function of these related homeoproteins, indicating divergent molecular mechanisms of action.
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ont., Canada N1G 2W1.
authors.forename: Shu-Hsuan Claire
authors.initials: SH
authors.lastname: Hsu
authors.forename: Babak
authors.initials: B
authors.lastname: Noamani
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Abernethy
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Levi
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bendall
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D020219:Chondrogenesis / Q000235:genetics; D005121:Extremities / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017385:Sequence Homology; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors