Pax1 and Pax9 activate Bapx1 to induce chondrogenic differentiation in the sclerotome.
We have previously shown that the paired-box transcription factors Pax1 and Pax9 synergistically act in the proper formation of the vertebral column. Nevertheless, downstream events of the Pax1/Pax9 action and their target genes remain to be elucidated. We show, by analyzing Pax1;Pax9 double mutant mice, that expression of Bapx1 in the sclerotome requires the presence of Pax1 and Pax9, in a gene dose-dependent manner. By using a retroviral system to overexpress Pax1 in chick presomitic mesoderm explants, we show that Pax1 can substitute for Shh in inducing Bapx1 expression and in initiating chondrogenic differentiation. Furthermore, we demonstrate that Pax1 and Pax9 can transactivate regulatory sequences in the Bapx1 promoter and that they physically interact with the Bapx1 promoter region. These results strongly suggest that Bapx1 is a direct target of Pax1 and Pax9. Together, we conclude that Pax1 and Pax9 are required and sufficient for the chondrogenic differentiation of sclerotomal cells.
Rodrigo
Isabel
I
GSF-National Research Center for Environment and Health, Institute of Developmental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
Hill
Robert E
RE
Balling
Rudi
R
Münsterberg
Andrea
A
Imai
Kenji
K
D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D020219:Chondrogenesis / Q000235:genetics / Q000502:physiology*; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D008969:Molecular Sequence Data; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors; D011401:Promoter Regions, Genetic; D013131:Spine / Q000196:embryology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C107965:Nkx3-2 protein, mouse; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; C070835:PAX1 transcription factor; D004247:DNA