DEFICIENT AND DELAYED PRIMARY PALATAL FUSION AND MESENCHYMAL BRIDGE FORMATION IN CLEFT LIP-LIABLE STRAINS OF MICE

During mammalian primary palate formation, the facial prominences enla rge around the nasal pit, fuse and then merge to give rise to the tiss ue of the upper lip and premaxillary region. The mechanisms involved i n successful primary palate formation and how they are affected in the cleft lip genotype remain poorly understood. The purpose of this stud y was to compare morphometrically internal development and growth of t he primary palate in five different strains of mice. Two of the strain s, BALB/cByJ, and C57BL/6J, have normal primary palate development, an d three of the strains, A/J, A/WySn, and CL/Fr, have stable frequencie s of cleft lip associated with genotype. In the present study, frequen cies of 4, 23, and 24%, respectively, were observed on day 13. For pal atal growth analysis, embryos were collected on days 10 and 11, staged by number of tail somites (TS), and the heads were photographed and s erially sectioned for measurement of primary palate components. The he ights of the epithelial seam and the mesenchyme bridge between the fac ial prominences were measured on serial sections and areas of contact were calculated. The position or depth of the maxillary prominence was determined from the number of frontal sections from its rip to the ro stral end of the nasal fin. Analysis of measurements showed that in cl eft lip strains enlargement of the epithelial seam and replacement of epithelia by a mesenchymal bridge were both delayed relative to somite stages. Measurements from day 11 embryos with complete failure of con tact were excluded from the growth analyses. The mesenchymal bridge fo rmed at 12-13 TS in noncleft strains, 14 TS in the A/J strain with low er cleft lip frequency, and 15-17 TS in A/WySn and CL/Fr strains with higher cleft lip frequency. Forward growth of the maxillary prominence was highly correlated with the primary palate measurements and mesenc hymal bridge formation in all strains. In both cleft and noncleft stra ins, the primitive choanae open at 18-20 TS and the medial nasal regio n narrows with advancing embryonic development. As a result, cleft lip -liable strains have a narrower window in development in which a robus t mesenchymal bridge must form, thus increasing the liability to cleft lip.