Effects of 13-cis-retinoic acid on hindbrain and craniofacial morphogenesis in long-tailed macaques (Macaca fascicularis)

Hindbrain and craniofacial development during early organogenesis was studi ed in normal and retinoic acid-exposed Macaca fascicularis embryos. 13-cis- retinoic acid impaired hindbrain segmentation as evidenced by compression o f rhombomeres I to 5. Immunolocalization with the Hoxb-1 gene product along with quantitative measurements demonstrated that rhombomere 4 was particul arly vulnerable to size reduction. Accompanying malformations of cranial ne ural crest cell migration patterns involved reduction and/or delay in pre- and post-otic placode crest cell populations that contribute to the pharyng eal arches and provide the developmental framework for the craniofacial reg ion. The first and second pharyngeal arches were partially fused and the se cond arch was markedly reduced in size. The otocyst was delayed in developm ent and shifted rostrolaterally relative to the hindbrain. These combined c hanges in the hindbrain, neural crest, and pharyngeal arches contribute to the craniofacial malformations observed in the retinoic acid malformation s yndrome manifested in the macaque fetus.