Trps1, a regulator of chondrocyte proliferation and differentiation, interacts with the activator form of Gli3.
Trps1, the gene mutated in human Tricho-Rhino-Phalangeal syndrome, represents an atypical member of the GATA-family of transcription factors. Here we show that Trps1 interacts with Indian hedgehog (Ihh)/Gli3 signaling and regulates chondrocyte differentiation and proliferation. We demonstrate that Trps1 specifically binds to the transactivation domain of Gli3 in vitro and in vivo, whereas the repressor form of Gli3 does not interact with Trps1. A domain of 185aa within Trps1, containing three predicted zinc fingers, is sufficient for interaction with Gli3. Using different mouse models we find that in distal chondrocytes Trps1 and the repressor activity of Gli3 are required to expand distal cells and locate the expression domain of Parathyroid hormone related peptide. In columnar proliferating chondrocytes Trps1 and Ihh/Gli3 have an activating function. The differentiation of columnar and hypertrophic chondrocytes is supported by Trps1 independent of Gli3. Trps1 seems thus to organize chondrocyte differentiation interacting with different subsets of co-factors in distinct cell types.
Wuelling
Manuela
M
Center for Medical Biotechnology, Department of Developmental Biology, University Duisburg-Essen, 45117 Essen, Germany.
Kaiser
Frank J
FJ
Buelens
Laetitia A
LA
Braunholz
Diana
D
Shivdasani
Ramesh A
RA
Depping
Reinhard
R
Vortkamp
Andrea
A
D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D003433:Crosses, Genetic; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000502:physiology; D012097:Repressor Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000074290:Zinc Finger Protein Gli3
D050980:GATA Transcription Factors; C465571:Gli3 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; C525953:Trps1 protein, mouse; D000074290:Zinc Finger Protein Gli3; D005982:Glutathione Transferase