Abstract
The effects of retinoic acid (RA) on craniofacial development during embryonic morphogenesis were examined using mouse whole embryo and cell cultures. In day 8 cultured embryos, RA caused significant embryonic growth retardation. Most in the development of the visceral arches. RA also inhibited the migration of cranial neural crest cells. In day 10 cultured embryos, RA produced a high percentage of embryos with median cleft lip and hypoplasia of the primary palatal processes. Autoradiogram showed a reduction in the size of the secondary palatal processes, pyknotic nuclei and a reduced number of labeled nuclei in mesenchyme of the nasal and maxillary processes in RA-exposed embryos. In mouse and human embryonic palatal mesenchymal cells, RA or its metabolites interfered with DNA synthesis and affected the cell proliferation, although RA treatment did not alter the incidence of chromosome aberrations and SCE even with metabolic activation. These findings indicate that RA plays an important role in normal and abnormal craniofacial development of mammalian embryos, especially palatal growth and differentiation.