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


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 C2-dependent domain containing 3 (C2CD3). Interestingly, our previous work identified a mutation in C2CD3 as the causal genetic lesion for the avian talpid2 mutant. Based on this common genetic etiology, we re-examined the talpid2 mutant for OFD-like phenotypes. We found that almost all phenotypes are conserved between talpid2 embryos and OFD patients. In light of this finding we utilized the talpid2 to examine the cellular basis for the craniofacial phenotypes present in OFD.


Using both in vivo and in vitro methods we analyzed specification, migration, proliferation and differentiation of cranial neural crest cells (CNCC) when C2CD3-dependent ciliogenesis was impacted.


Our studies suggest that whereas disruptions of C2CD3-dependent ciliogenesis did not affect CNCC specification or proliferation, it did affect CNCC migration and differentiation. Migrating talpid2 CNCCs were more disperse than control CNCCs and their migration was impaired. Furthermore, talpid2 CNCC derived cartilages are larger relative to controls.


Taken together, these findings suggest that the avian talpid2 mutant is a bona fide, novel model for OFD and that aberrant CNCC migration and differentiation could contribute to the pathology of C2CD3-dependent human OFD.

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Correspondence to SA Brugmann.

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  • Calcium
  • Developmental Biology
  • Crest
  • Cardiac Defect
  • Molar Tooth