Journal of Craniofacial Surgery

Skip Navigation LinksHome > January 2012 - Volume 23 - Issue 1 > Calvarial Cleidocraniodysplasia-Like Defects With ENU-Induce...
Journal of Craniofacial Surgery:
doi: 10.1097/SCS.0b013e318240c8c4
Original Articles

Calvarial Cleidocraniodysplasia-Like Defects With ENU-Induced Nell-1 Deficiency

Zhang, Xinli MD, PhD*†; Ting, Kang DMD, DMedSci*†‡; Pathmanathan, Dharmini DDS, PhD; Ko, Theodore DDS; Chen, Weiwei BS*; Chen, Feng PhD*; Lee, Haofu PhD; James, Aaron W. MD*; Siu, Ronald K. MS§; Shen, Jia PhD*; Culiat, Cymbeline T. PhD; Soo, Chia MD

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Abstract: Nell-1, first identified by its overexpression in synostotic cranial sutures, is a novel osteoinductive growth and differentiation factor. To further define Nell-1’s role in craniofacial patterning, we characterized defects of the ENU-induced Nell-1–deficient (END) mice, focusing on both intramembranous and endochondral cranial bones. Results showed that calvarial bones of neonatal END mice were reduced in thickness and density, with a phenotype resembling calvarial cleidocraniodysplasia. In addition, a global reduction in osteoblast markers was observed, including reductions in Runx2, alkaline phosphatase, and osteocalcin. Remarkably, detailed analysis of endochondral bones showed dysplasia as well. The chondrocranium in the END mouse showed enrichment for early, proliferating Sox9+ chondrocytes, whereas in contrast markers of chondrocytes maturation were reduced. These data suggest that Nell-1 is an important growth factor for regulation of osteochondral differentiation, by regulating both Runx2 and Sox9 expression within the calvarium. In summary, Nell-1 is required for normal craniofacial membranous and endochondral skeletal development.

© 2012 Mutaz B. Habal, MD

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