Multiple roles for retinoid signaling in craniofacial development.

Retinoic acid (RA) signaling plays multiple essential roles in development of the head and face. Animal models with mutations in genes involved in RA signaling have enabled understanding of craniofacial morphogenic processes that are regulated by the retinoid pathway. During craniofacial morphogenesis RA signaling is active in spatially restricted domains defined by the expression of genes involved in RA production and RA breakdown. The spatial distribution of RA signaling changes with progressive development, corresponding to a multiplicity of craniofacial developmental processes that are regulated by RA. One important role of RA signaling occurs in the hindbrain. There RA contributes to specification of the anterior-posterior (AP) axis of the developing CNS and to the neural crest cells (NCC) which form the bones and nerves of the face and pharyngeal region. In the optic vesicles and frontonasal process RA orchestrates development of the midface, eyes, and nasal airway. Additional roles for RA in craniofacial development include regulation of submandibular salivary gland development and maintaining patency in the sutures of the cranial vault.