Relationship between hindbrain segmentation, neural crest cell migration and branchial arch abnormalities in rat embryos exposed to fluconazole and retinoic acid in vitro.

Fluconazole (FLUCO) and retinoic acid (RA) can perturb morphogenesis of the branchial apparatus in rodent embryos exposed in vitro. The aim of the present study was to compare the effects induced by in vitro exposure to FLUCO or to RA on rhombomere organisation, neural crest cell (NCC) migration and cranial nerve differentiation using specific antibodies. For this purpose 9.5 d.p.c. rat embryos were exposed to teratogenic concentrations of FLUCO or RA; another group was exposed to no-effect concentrations of both agents. Expression of Hox-b1 and Krox20 (markers of specific rhombomeres) was altered after FLUCO and RA exposure. Furthermore, FLUCO and RA showed a synergistic effect. These results suggest that the observed branchial abnormalities are due to anomalous NCC migration related to incorrect organisation of specific rhombomeres.