Origin stories of neural crest roles in craniofacial development: A tale of the meninges

As developmental biologists, we tell origin stories to explain differences in vertebrate craniofacial form and complexity. Some of these differences are linked to diseases, notably of patients born with congenital malformations, many of them syndromic. These defective processes impede proper neural crest cell migration, differentiation, and patterning of bones, cartilage, joints, muscle and other connective tissues, including of the head. For example, a rare form of holoprosencephaly called cyclopia is a particular quandary in its diverse presentation. This syndromic congenital disease includes lost brain frontal lobe septation and development of a single eye. Subsequent craniofacial midline defects include frontal suture synostosis, absent nose and medial maxilla, and a restructuring of facial bones to accommodate one eye. The meningeal tissues in contact with both the underlying brain and the overlying calvarial bone are derived at least in part from neural crest cells. This Perspectives piece re-examines communication between the neural crest cell-brain axis, explores the direct involvement of the meninges in this communication process, and proposes an expanded origin story about the etiology of craniofacial patterning and disease.