Osterix is required for cranial neural crest-derived craniofacial bone formation

Abstract

Osx plays essential roles in regulating osteoblast and chondrocyte differentiation, and bone formation during mouse skeletal development. However, many questions remain regarding the requirement for Osx in different cell lineages. In this study, we asked whether Osx is required for craniofacial bone formation derived from cranial neural crest (CNC) cells. The Osx gene was conditionally inactivated in CNC-derived cells using a Wnt1-Cre recombination system. Neural crest-specific inactivation of Osx resulted in the complete absence of intramembranous skeletal elements derived from the CNC, and CNC-derived endochondral skeletal elements were also affected by Osx inactivation. Interestingly, Osx inactivated CNC-derived cells, which were recapitulated by lacZ expression, occupied the same regions of craniofacial skeletal elements as observed for controls. However, cells lost their osteogenic ability to differentiate into functional osteoblasts by Osx inactivation. These results suggest that Osx is important for craniofacial bone formation by CNC-derived cells. This finding provides novel insights of the regulation of craniofacial development by the gene network and transcription factors, and the understanding of human diseases caused by neural crest developmental abnormalities.

Negative regulation of Endothelin signaling by SIX1 is required for proper maxillary development

“…In E12.5 control embryos, Osterix (Osx), a transcription factor associated with early osteogenesis (Baek et al, 2013;Nakashima et al, 2002), was weakly expressed in the posterior maxillary region (Fig. 7A).…”

Mandible and Tongue Development

“…Dlx5 , which is expressed from the early stages, induces the expression of Runx2 . Runx2 (also known as cbfa1) is one of the first genes expressed by mesenchymal cells committed to the osteogenic lineage and is required for differentiation of mesenchymal cells into preosteoblasts (Baek, Kim, de Crombrugghe, & Kim, 2013). Ablation of Runx2 causes generalized malformations of the skeleton.…”

“…Osterix ( Osx or SP7 ), a Runx2 downstream gene, is required for the differentiation of preosteoblasts into mature osteoblasts and is specifically expressed in all osteoblasts (Zhang, 2010). Mutation of Osx in CNCC derivatives leads to a tiny and rudimentary mandible although the MC is unaffected (Baek et al, 2013). This finding suggests again that the development of the mandibular bone and MC are not interdependent.…”

BMP Signaling in the Development and Regeneration of Cranium Bones and Maintenance of Calvarial Stem Cells

“…Neural crest-specific inactivation of Osx resulted in a complete absence of intramembranous skeletal bones that derived from the CNC. Besides, the CNCderived endochondral skeletal bones were also affected (Baek et al, 2013). Taken together, the data suggested that a precise responsiveness to BMP signaling in CNC cells is crucial for the proper morphogenesis of the calvaria, and the BMP signaling can be counted on for the superior osteogenic potential in CNCderived bones.…”