PUBLICATION

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

Authors
Zhu, J., Wang, H.T., Chen, Y.R., Yan, L.Y., Han, Y.Y., Liu, L.Y., Cao, Y., Liu, Z.Z., Xu, H.A.
ID
ZDB-PUB-200820-2
Date
2020
Source
Neuroscience Bulletin   36(9): 1023-1034 (Journal)
Registered Authors
Cao, Ying, Xu, Hong
Keywords
Cerebellum, Development, Granule cell, Joubert syndrome, Purkinje cell, Wnt, arl13b
MeSH Terms
  • ADP-Ribosylation Factors/metabolism*
  • Abnormalities, Multiple*
  • Animals
  • Cerebellum/abnormalities
  • Cerebellum/growth & development*
  • Eye Abnormalities*
  • Gene Knockdown Techniques
  • Gene Knockout Techniques
  • Kidney Diseases, Cystic*
  • Purkinje Cells
  • Retina/abnormalities
  • Retina/metabolism
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism*
PubMed
32812127 Full text @ Neurosci. Bull.
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.
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