The Joubert Syndrome Gene arl13b is Critical for Early Cerebellar Development in Zebrafish
1 Institute of Life Science, Nanchang University, Nanchang 330031, China
2 School of Life Sciences, Nanchang University, Nanchang 330031, China
3 Jiangxi Provincial Collaborative Innovation Center for Cardiovascular, Digestive and Neuropsychiatric Diseases, Nanchang 330031, China
4 Department of Molecular and Cell Biology, Tongji University School of Life Sciences and Technology, Shanghai 200092, China
5 Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou 510006, China
Abstract
Joubert syndrome is characterized by unique malformation of the cerebellar vermis. More than thirty Joubert syndrome genes have been identified, including ARL13B. However, its role in cerebellar development remains unexplored. We found that knockdown or knockout of arl13b impaired balance and locomotion in zebrafish larvae. Granule cells were selectively reduced in the corpus cerebelli, a structure homologous to the mammalian vermis. Purkinje cell progenitors were also selectively disturbed dorsomedially. The expression of atoh1 and ptf1, proneural genes of granule and Purkinje cells, respectively, were selectively down-regulated along the dorsal midline of the cerebellum. Moreover, wnt1, which is transiently expressed early in cerebellar development, was selectively reduced. Intriguingly, activating Wnt signaling partially rescued the granule cell defects in arl13b mutants. These findings suggested that Arl13b is necessary for the early development of cerebellar granule and Purkinje cells. The arl13b-deficient zebrafish can serve as a model organism for studying Joubert syndrome.
Keywords
Joubert syndrome; arl13b; Cerebellum; Development; Granule cell; Purkinje cell; Wnt
