Role of genes involved in midfacial morphogenesis

Orofacial clefting is the most common congenital anomaly that affects 1/700 Saskatchewan babies. Midfacial clefting, a subset of orofacial clefting, affects the development of the nasal septum and the medial nasal prominences. However, less is known about the mechanisms underlying midfacial clefting.  Our lab models midfacial clefting using two different mouse lines – the Unicorn and the Prickle1^Beetlejuice (Prickle1^Bj)  mouse lines. We did cell lineage tracing to track Sox9 expressing chondrocytes in early development of Unicorn embryos and observed decreased Sox9 expression in the medial nasal prominence (mnp) of the mutants. We also performed whole mount in-situ hybridization experiments on wildtype and mutant embryos to compare the expression domains of the morphogen Sonic hedgehog (Shh) and the medial nasal prominence specifier Alx3. The results demonstrate the decreased Alx3 expression in the proximal regions of the frontonasal prominences and wider medial expression domains of Shh in the Unicorn and the Prickle1^Beetlejuice mutants. Together these results suggest the roles of  Alx3 and Shh in the proper merging of the midline.