Pathogenesis of cleft lip and its relation to embryonic face shape in A/J and C57BL mice

Abstract A comparison was made of early face embryology in the inbred A/J mouse strain with a spontaneous frequency of about 12% cleft lip and the C57BL/6J strain which virtually never has cleft lip. From the time of their appearance the medial nasal, lateral nasal and maxillary processes are connected by an isthmus. Subsequently there is fusion between the adjacent epithelia of medial and lateral nasal processes. Failure of this fusion, followed by breakdown of the isthmus, results in cleft lip. Just before and when the adjacent epithelia of medial nasal and lateral nasal processes meet and fuse at the posterior end of the nasal pit, the medial nasal processes of A/J embryos were more prominent, more medially placed, and diverged less than those of C57BL/6J. It is suggested that (a) cleft lip is a threshold character or quasi‐continuous variant such that a very slight change in the divergence of the medial nasals leads to their partial or complete lack of fusion with the lateral nasals. This is followed by a lack of fusion of medial and maxillary processes, and a complete or partial breakdown of the isthmus, resulting in a cleft lip; (b) the strain differences in type of aspirin‐induced cleft lip and in topography and growth of the facial processes between the two strains are causally related to the A/J predisposition to cleft lip.