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.

中文翻译：

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乔伯特综合症基因arl13b对于斑马鱼的早期小脑发育至关重要。

Joubert综合征的特征是小脑ver部畸形。已经鉴定出三十多种Joubert综合征基因，包括ARL13B。然而，其在小脑发育中的作用尚待探索。我们发现敲除或敲除arl13b会损害斑马鱼幼虫的平衡和运动能力。小脑中的颗粒细胞被选择性还原，该结构与哺乳动物的mis同源。浦肯野细胞祖细胞也有选择地被背部扰动。沿小脑背中线选择性下调了atoh1和ptf1的表达，分别是颗粒细胞和Purkinje细胞的前体基因。此外，wnt1在小脑发育早期短暂表达的，被有选择地减少。有趣的是，激活Wnt信号可部分挽救arl13b突变体中的颗粒细胞缺陷。这些发现表明，Arl13b对于小脑颗粒和浦肯野细胞的早期发育是必需的。该arl13b缺陷型斑马鱼可作为研究茹贝尔综合征模型生物。