Hes1 Is Required for the Development of Craniofacial Structures Derived From Ectomesenchymal Neural Crest Cells

Abstract

The cranial neural crest cells contribute extensively to the formation of skeletogenic mesenchyme in the head and neck. Hes1 functions as a repressor of basic helix-loop-helix transcription factors and is implicated in controlling the maintenance of undifferentiated cells and the timing of cell differentiation. We show here that Hes1 homozygous null mutant mice exhibit multiple craniofacial malformations including calvaria agenesis, defective anterior cranial base, shortened maxilla and mandible, and abnormal palate and tongue. In the null mutant cranium, the calvarial bones, meninges including the dura mater and skin were not formed, and the brain was therefore exposed without the outer cover. The defective anterior cranial base in the mutants was attributable to the lack of presphenoid bone and the flexed cranial base angle, which was in contrast with the flat cranial base of wild-type mice. Furthermore, in the null mutants, palatal shelf growth was impaired because of the early elevation of the palatal shelves, resulting in a narrow palate and oral cavity, which were consistently associated with a small size of the tongue. These craniofacial anomalies could be the result of the defective development of neural crest cells. Taken together, it is supposed that Hes1 signaling plays an essential role in regulating the development of various craniofacial structures derived from the cranial neural crest cells.