KIF7 deletion in a mouse model of human ciliopathy alters cerebral cortex development

Mutations of KIF7, a key ciliary component of the Sonic hedgehog (SHH) pathway, are associated in humans with malformations of the cerebral cortex and clinical features suggestive of cortical dysfunction. In both humans and mice, KIF7 regulates the processing of GLI-A and GLI3-R transcription factors in a SHH-dependent manner. To understand the pathological mechanisms involved in cerebral cortex defects, we took advantage of a Kif7 −/− mouse model in which the cellular mechanisms leading to the corpus callosum agenesis had already been investigated ([Putoux et al, 2019][1]). We observed a stronger impact of the Kif7 deletion on the development of the mouse dorsal cortex, in agreement with the important role of GLI3-R in the pattering of the dorsal telencephalon. The intermediate progenitor layer and cortical plate no longer segregated, preventing the formation of the intermediate zone, and subplate cells were missing. Corticofugal axons did not develop properly leading to a delayed colonization of the telencephalon by thalamo-cortical axons. These structural defects altered the cortical distribution of GABAergic interneurons generated in the basal telencephalon, which moreover exhibited intrinsic migration defects resembling those of control interneurons treated with cyclopamine. These migratory defaults suggested that the SHH pathway can no longer be activated in cortical interneurons generated in the ventral telencephalon of Kif7 -/- mice. ### Competing Interest Statement The authors have declared no competing interest. [1]: #ref-64