The chick transcriptional repressor Nkx3.2 acts downstream of Shh to promote BMP-dependent axial chondrogenesis.
Previously, we demonstrated that Shh acts early in the development of the axial skeleton, to induce a prochondrogenic response to later BMP signaling. Here, we demonstrate that somitic expression of the transcription factor Nkx3.2 is initiated by Shh and sustained by BMP signals. Misexpression of Nkx3.2 in somitic tissue confers a prochondrogenic response to BMP signals. The transcriptional repressor activity of Nkx3.2 is essential for this factor to promote chondrogenesis. Conversely, a "reverse function" mutant of Nkx3.2 that has been converted into a transcriptional activator inhibits axial chondrogenesis in vivo. We conclude that Nkx3.2 is a critical mediator of the actions of Shh during axial cartilage formation, acting to inhibit expression of factors that interfere with the prochondrogenic effects of BMPs.
Murtaugh
L C
LC
Department of Biological Chemistry and Molecular Pharmacy, Harvard Medical School, Boston, Massachusetts 02115, USA.
Zeng
L
L
Chyung
J H
JH
Lassar
A B
AB
D053674:Aggrecans; D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019556:COS Cells; D002352:Carrier Proteins; D002642:Chick Embryo; D020219:Chondrogenesis / Q000502:physiology*; D024081:Collagen Type IX / Q000378:metabolism; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins / Q000378:metabolism; D004627:Embryonic Induction; D016326:Extracellular Matrix Proteins; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter / Q000235:genetics; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D037181:Lectins, C-Type; D051761:Paired Box Transcription Factors; D011506:Proteins / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099176:Noggin Protein
D053674:Aggrecans; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D024081:Collagen Type IX; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D037181:Lectins, C-Type; D051761:Paired Box Transcription Factors; D011506:Proteins; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099176:Noggin Protein; C070835:PAX1 transcription factor