Using the talpid2 as novel model for determining the cellular and molecular etiology of Oral-facial-digital syndrome

Objective Oral-facial-digital syndrome (OFD) is a ciliopathy characterized by craniofacial abnormalities including cleft lip/palate, glossal defects, and absent/dysmorphic or supernumerary teeth. In addition, these patients have several other abnormalities typical of a ciliopathy including polysyndactyly, hypoplasia of the cerebellar vermis (molar tooth sign), cardiac defects and polycystic kidneys. Recently a subset of OFD cases have been linked to mutations in the centriolar protein, calcium C2dependent domain containing 3 (C2CD3). Interestingly, our previous work identified a mutation in C2CD3 as the causal genetic lesion for the avian talpid mutant. Based on this common genetic etiology, we re-examined the talpid mutant for OFD-like phenotypes. We found that almost all phenotypes are conserved between talpid embryos and OFD patients. In light of this finding we utilized the talpid to examine the cellular basis for the craniofacial phenotypes present in OFD.