Brugmann Lab
Talpid2 for craniofacial ciliopathies

Using the avian model talpid2 to study human craniofacial ciliopathies

talpid2 (ta2) is a naturally occurring avian ciliopathic mutant with a myriad of craniofacial defects, including a dysmorphic frontonasal prominence, facial clefting, hypoplastic maxillary prominences, incomplete fusion of the primary palate and hypoglossia. Our recent work determined that the ta2 mutation affected ciliogenesis via a deletion mutation in C2CD3 (Chang et al., 2014), a centriolar protein required for ciliogenesis. Concurrently, mutations in C2CD3 were found in a subset of individuals with the human craniofacial ciliopathy oral-facial-digital syndrome (OFD) (Thauvin-Robinet et al., 2014). We utilize the avian ta2 mutant to determine the cellular and molecular etiology of the common oral-facial phenotypes present in OFD patients. Specifically, we examine how C2CD3-dependent ciliogenesis affects the development of cranial neural crest cells, the progenitors of the facial skeleton.

Whole mount image of a day 10 talpid2 mutant embryo.
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The avian mutant ta2 phenocopies human OFD. (A-H) Whole mount images of day 10 control and ta2 embryos. (A, B) Lateral view of control and ta2 face with cleft lip (B) denoted by dotted white line. (C, D) Ventral view of control and ta2 palate with cleft primary palate (D) denoted by white arrows. Compare width of naturally occurring cleft of the secondary palate in (C) and pathological cleft in (D); dotted white lines. (E, F) Dorsal view of control and ta2 mandible. (F) ta2 embryos exhibit hypoglossia (compare dotted white lines in (E) and (F)). (G, H) Lateral view of control and ta2 forelimb. (H) ta2 embryos exhibit severe polydactyly. (I, J) Whole mount image of day 13 control and ta2 kidneys with polycystic kidneys denoted by black asterisks (J). (K, L) H&E staining on day 13 control and ta2 kidneys with cysts marked with black asterisks (L). (M, N) Micro-CT images of day 13 control and ta2 cerebella with folia numbered and fourth ventricle denoted (fv).
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