The Joubert Syndrome Gene arl13b is Critical for Early Cerebellar Development in Zebrafish

AbstractJoubert syndrome is characterized by unique malformation of the cerebellar vermis. More than thirty Joubert syndrome genes have been identified, includingARL13B. However, its role in cerebellar development remains unexplored. We found that knockdown or knockout ofarl13b 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 ofatoh1 andptf1, 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 inarl13b mutants. These findings suggested that Arl13b is necessary for the early development of cerebellar granule and Purkinje cells. Thearl13b-deficient zebrafish can serve as a model organism for studying Joubert syndrome.
Source: Neuroscience Bulletin - Category: Neuroscience Source Type: research