Reference - Detail
| RRC ID | 36953 |
|---|---|
| Author | Yoshida M, Hata K, Takashima R, Ono K, Nakamura E, Takahata Y, Murakami T, Iseki S, Takano-Yamamoto T, Nishimura R, Yoneda T. |
| Title | The transcription factor Foxc1 is necessary for Ihh-Gli2-regulated endochondral ossification. |
| Journal | Nat Commun |
| Abstract |
Indian hedgehog (Ihh) regulates endochondral ossification in both a parathyroid hormone-related protein (PTHrP)-dependent and -independent manner by activating transcriptional mediator Gli2. However, the molecular mechanisms underlying these processes remain elusive. Here by using in vivo microarray analysis, we identify forkhead box C1 (Foxc1) as a transcriptional partner of Gli2. Foxc1 stimulates expression of Ihh target genes, including PTHrP and Col10a1, through its physical and functional interaction with Gli2. Conversely, a dominant negative Foxc1 inhibits the Ihh target gene expression. In a spontaneous loss of Foxc1 function mouse (Foxc1(ch/ch)), endochondral ossification is delayed and the expression of Ihh target genes inhibited. Moreover, the pathological Foxc1 missense mutation observed in the Axenfeld-Rieger syndrome impairs Gli2-Foxc1 association as well as Ihh function. Our findings suggest that Foxc1 is an important transcriptional partner of Ihh-Gli2 signalling during endochondral ossification, and that disruption of the Foxc1-Gli2 interaction causes skeletal abnormalities observed in the Axenfeld-Rieger syndrome. |
| Volume | 6 |
| Pages | 6653 |
| Published | 2015-3-26 |
| DOI | 10.1038/ncomms7653 |
| PII | ncomms7653 |
| PMID | 25808752 |
| MeSH | Animals Anterior Eye Segment / abnormalities* COS Cells Chlorocebus aethiops Chondrocytes / metabolism* Collagen Type X / genetics Collagen Type X / metabolism Embryo, Mammalian Eye Abnormalities / genetics* Eye Diseases, Hereditary Forkhead Transcription Factors / genetics* Gene Expression Regulation, Developmental / genetics* HEK293 Cells Hedgehog Proteins / genetics* Hedgehog Proteins / metabolism Humans Kruppel-Like Transcription Factors / genetics* Kruppel-Like Transcription Factors / metabolism Mice Mice, Transgenic Mutation, Missense Osteogenesis / genetics* Parathyroid Hormone-Related Protein / genetics Parathyroid Hormone-Related Protein / metabolism Real-Time Polymerase Chain Reaction Transcriptional Activation Zinc Finger Protein Gli2 |
| IF | 12.121 |
| Times Cited | 29 |
| WOS Category | MULTIDISCIPLINARY SCIENCES |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | COS-7(RCB0539) 293(RCB1637) |