RRC ID 77582
Author Funato N, Srivastava D, Shibata S, Yanagisawa H.
Title TBX1 Regulates Chondrocyte Maturation in the Spheno-occipital Synchondrosis.
Journal J Dent Res
Abstract The synchondrosis in the cranial base is an important growth center for the craniofacial region. Abnormalities in the synchondroses affect the development of adjacent regions, including the craniofacial skeleton. Here, we report that the transcription factor TBX1, the candidate gene for DiGeorge syndrome, is expressed in mesoderm-derived chondrocytes and plays an essential and specific role in spheno-occipital synchondrosis development by inhibiting the expression of genes involved in chondrocyte hypertrophy and osteogenesis. In Tbx1-deficient mice, the spheno-occipital synchondrosis was completely mineralized at birth. TBX1 interacts with RUNX2, a master molecule of osteoblastogenesis and a regulator of chondrocyte maturation, and suppresses its transcriptional activity. Indeed, deleting Tbx1 triggers accelerated mineralization due to accelerated chondrocyte differentiation, which is associated with ectopic expression of downstream targets of RUNX2 in the spheno-occipital synchondrosis. These findings reveal that TBX1 acts as a regulator of chondrocyte maturation and osteogenesis during the spheno-occipital synchondrosis development. Thus, the tight regulation of endochondral ossification by TBX1 is crucial for the normal progression of chondrocyte differentiation in the spheno-occipital synchondrosis.
Volume 99(10)
Pages 1182-1191
Published 2020-9-1
DOI 10.1177/0022034520925080
PMID 32442036
MeSH Animals Cell Differentiation Chondrocytes* Chondrogenesis* Mice Occipital Bone* Osteogenesis* Sphenoid Bone T-Box Domain Proteins* / genetics T-Box Domain Proteins* / physiology
IF 4.914
Mice RBRC01145