The basal body protein Ofd1 is essential for dorso-ventral patterning and axoneme elongation in the embryonic cortex

Oral-facial-digital type I syndrome (OFDI; OMIM 311200) is an X-linked dominant developmental ciliopathy with lethality in males. Female patients present malformations of the oral cavity, face, digits and central nervous system. The human disease gene OFD1 encodes a centrosome/basal body protein. In the present study we analyzed the neurological phenotype in mouse development of Ofd1 inactivation. Given that male mutant die very early during gestation we focused our analysis on heterozygous female at E12.5 and due to X-inactivation we observed a high degree of variability in phenotypes. The analysis of neurological defects in Ofd1 severe mutant embryos revealed that the basal body protein has a crucial role in the brain development, controlling dorso-ventral patterning of the forebrain. Ultrastructural studies demonstrated that Ofd1 inactivation affected ciliogenesis in severe mutant embryos leading to the absence of ciliary axonemes despite the presence of mature basal bodies correctly oriented and docked. Planar cell polarity pathway and cytoskeletal organization were defective in our mouse model most likely due to the lack of ciliary axonemes. The present study shed light on the role of the basal body protein Ofd1 in development and in ciliogenesis.