Morphometric studies of normal and abnormal primary palate formation in noncleft and cleft lip strains of mice
Creators: name: Wang, Kang-Yee
Publisher: name: University of British Columbia
Year: 2009

description: Growth and development of the primary palate in the human embryo is complicated. Failure of the fusion of the maxillary prominence, with the lateral nasal and the medial nasal prominences results in cleft lip. Although many qualitative descriptions have been published on both normal and abnormal palatogenesis, there is little definitive information about mechanisms of primary palate formation. This study will address mechanisms using the mouse as the experimental model. The embryogenesis of primary palate of mouse is similar to that of human and spontaneous cleft lip is associated with genotype in both. Therefore the mouse provides an experimental model for studying primary palatogenesis. The purpose of my research was to compare primary palate development in different strains of mice. Two of the strains studied, BALB/cByJ and C57BLJ6J, have normal primary palate development, and three of the strains studied, A/J, AIWySn and CL/Fr, have stable frequencies of cleft lip. The first part of this study was to determine the cleft lip frequency and the resorption rate of the three cleft lip strains of mice. The results confirmed previous observations that NJ has a lower frequency of cleft lip and a higher resorption rate than that of A/WySn and CL/Fr. The purpose of second part of this study was to determine the stage of body development and the chronological age at which primary palatogenesis takes place in these five strains. The results showed that in each strain, the number of tail so in that strain. Somite development in the strains with genetic cleft lip liability was approximately twelve hours later than in the C57BLJ6J strain. However, in the noncleft BALB/cByJ strain, the somite was also twelve hours later than in C57BLI6J. Thus, delayed chronological development appears not to be a factor contributing to cleft lip malformation. In the third part of the study, the phases of primary palatogenesis were compared in the noncleft and cleft lip strains. The results showed fusion of the epithelia to form the nasal fin and replacement of the epithelial seam by mesenchyme was delayed in cleft lip strains relative to tail somite stages. The strains with higher cleft lip frequency, A/WySn and CL/Fr, were more delayed than the NJ strain with lower cleft lip frequency. The time of replacement of the nasal fin by mesenchyme occurred at about 12-13 tail somites in noncleft strains, 14 tail somites in NJ, 15 tail somites in NWySn and 16 tail somites in CL/Fr. Forward growth of the maxillary prominence had the same pattern as mesenchymal replacement in the strains. The position of the maxillary prominence was highly correlated with the size of the nasal fin and the mesenchymal component in all strains. One major gene could explain this delayed formation in cleft lip strains and maternal effect could explain the more delayed formation in NWySn and CL/Fr than in NJ strain. The purpose of the fourth part of this study was to determine the tail somite stage when the oronasal membrane ruptures to form the primary choana dorsal to the primary palate. A definitive primary palate is established as a consequence of this rupture. Primary choana formation occurred at 18 tail somites in CL/Fr and 20 tail somites in C57BLJ6J. This earlier occurrence in CL/Fr than in C57BL/6J appears to provide a more limited developmental interval for mesenchymal replacement and enlargement in the cleft lip strain. A multifactorial threshold model was suggested from this study. The tail somite stage of mesenchymal replacement is applied as a scale of liability for the cleft lip malformation. Unfavorable growth may move embryos toward the threshold and result in an increased incidence of cleft lip. The threshold may be affected by the timing of primary choana formation mites was highly correlated with development of primary palate