Temporospatial regulation of intraflagellar transport is required for the endochondral ossification in mice.
Dev Biol
; 482: 91-100, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-34929174
ABSTRACT
Ciliogenic components, such as the family of intraflagellar transport (IFT) proteins, are recognized to play key roles in endochondral ossification, a critical process to form most bones. However, the unique functions and roles of each IFT during endochondral ossification remain unclear. Here, we show that IFT20 is required for endochondral ossification in mice. Utilizing osteo-chondrocyte lineage-specific Cre mice (Prx1-Cre and Col2-Cre), we deleted Ift20 to examine its function. Although chondrocyte-specific Ift20 deletion with Col2-Cre mice did not cause any overt skeletal defects, mesoderm-specific Ift20 deletion using Prx1-Cre (Ift20Prx1-Cre) mice resulted in shortened limb outgrowth. Primary cilia were absent on chondrocytes of Ift20Prx1-Cre mice, and ciliary-mediated Hedgehog signaling was attenuated in Ift20Prx1-Cre mice. Interestingly, loss of Ift20 also increased Fgf18 expression in the perichondrium that sustained Sox9 expression, thus preventing endochondral ossification. Inhibition of enhanced phospho-ERK1/2 activation partially rescued defective chondrogenesis in Ift20 mutant cells, supporting an important role for FGF signaling. Our findings demonstrate that IFT20 is a critical regulator of temporospatial FGF signaling that is required for endochondral ossification.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
/
Proteínas de Transporte
/
Cílios
/
Deformidades Congênitas dos Membros
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Condrogênese
Limite:
Animals
Idioma:
En
Revista:
Dev Biol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos