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J Craniofac Surg. 2012 Jan;23(1):61-6. doi: 10.1097/SCS.0b013e318240c8c4.

Calvarial cleidocraniodysplasia-like defects with ENU-induced Nell-1 deficiency.

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  • 1Dental and Craniofacial Research Institute, Section of Orthodontics, School of Dentistry, UCLA and Orthopaedic Hospital Department of Orthopedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, California 90095, USA.

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.

PMID:
22337375
[PubMed - indexed for MEDLINE]
PMCID:
PMC3282020
Free PMC Article
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