Ofd1 controls dorso-ventral patterning and axoneme elongation during embryonic brain development.

Ofd1 controls dorso-ventral patterning and axoneme elongation during embryonic brain development.

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Oral-facial-digital type I syndrome (OFDI) is a human X-linked dominant-male-lethal developmental disorder caused by mutations in the OFD1 gene.Similar to other inherited disorders bilstein shocks jeep xj associated to ciliary dysfunction OFD type I patients display neurological abnormalities.We characterized the neuronal phenotype that results from Ofd1 inactivation in early phases of mouse embryonic development and at post-natal stages.We determined that Ofd1 plays a crucial role in forebrain development, and in particular, in the control of dorso-ventral patterning and early corticogenesis.We observed abnormal activation of Sonic hedgehog (Shh), a major pathway modulating brain development.

Ultrastructural studies demonstrated that early Ofd1 inactivation results in the absence of feline 1-hcpch vaccine ciliary axonemes despite the presence of mature basal bodies that are correctly orientated and docked.Ofd1 inducible-mediated inactivation at birth does not affect ciliogenesis in the cortex, suggesting a developmental stage-dependent role for a basal body protein in ciliogenesis.Moreover, we showed defects in cytoskeletal organization and apical-basal polarity in Ofd1 mutant embryos, most likely due to lack of ciliary axonemes.Thus, the present study identifies Ofd1 as a developmental disease gene that is critical for forebrain development and ciliogenesis in embryonic life, and indicates that Ofd1 functions after docking and before elaboration of the axoneme in vivo.