| RRC ID |
36953
|
| 著者 |
Yoshida M, Hata K, Takashima R, Ono K, Nakamura E, Takahata Y, Murakami T, Iseki S, Takano-Yamamoto T, Nishimura R, Yoneda T.
|
| タイトル |
The transcription factor Foxc1 is necessary for Ihh-Gli2-regulated endochondral ossification.
|
| ジャーナル |
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.
|
| 巻・号 |
6
|
| ページ |
6653
|
| 公開日 |
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
|
| 引用数 |
29
|
|
WOS 分野
|
MULTIDISCIPLINARY SCIENCES
|
| リソース情報 |
| ヒト・動物細胞 |
COS-7(RCB0539)
293(RCB1637) |
