Mitotic index in mouse embryos with 6-aminonicotinamide-induced and inherited cleft lip.

Abstract

Three types of cleft lip were studied histologically before and during lip formation in mouse embryos. C57BL/6 embryos observed near term following treatment with 6-aminonicotinamide (6AN) at gestation D9/12 (vp day = day 0) had 18% median cleft lip. Treated embryos observed at D10 and D11 showed retarded somite and nasal placode development. Sections at lip closure time showed marked reduction of medial and some reduction of lateral nasal processes, and the mitotic index was significantly reduced in the nasal area on D10 and D11 but less consistently in the neural area. 6AN-treatment on D10/8, caused 22% lateral cleft lip. Treated embryos showed initial retardation of somite and nasal placode development that became normal by D11/14. Sections showed reduction of the medial and lateral nasal processes, and less organized denser nasal ectoderm. The mitotic index was significantly reduced in the nasal and neural areas on D10 and D11. In crosses having the major gene mutation dancer (Dc) 20% of embryos had lateral cleft lip and potential cleft lip mutant embryos showed reduced lateral and medial nasal processes. Mitotic index was not reduced in the nasal area but it was in the neural area. The CL/Fr strain, with a predisposing face shape in which 26% of the embryos have cleft lip of multifactorial origin, had a mitotic index similar to that of C57BL/6 (0% cleft lip) at lip closure time, D11/14, and prominent medial nasal processes. It is postulated that 6AN-induced median cleft lip is due to reduced cell proliferation in and size of the medial nasal processes; 6AN-induced lateral cleft lip to reduced cell proliferation and reduced medial and lateral nasal processes and dancer lateral cleft lip to reduction of the medial nasals.