Jagged1 ablation results in cerebellar granule cell migration defects and depletion of Bergmann glia

Developmental Neuroscience
Mathias WellerVerdon Taylor

Abstract

Jagged1 is a ligand for members of the Notch family of receptors. Mutations in the human JAG1 gene are the major cause of Alagille syndrome, an autosomal dominant disorder affecting the liver, heart, eye, skeleton, kidneys, and craniofacial structures. Although expressed throughout mammalian embryonic development and in the adult, the function of Jagged1 in the central nervous system is not clear. Jagged1 is broadly expressed in the cerebellum suggesting an important role in Notch signaling. In order to address the function of Jagged1 in the mouse central nervous system, we have inactivated the Jag1 gene in the cerebellar primordium at mid-embryogenesis. Loss of Jagged1 results in aberrant granule cell migration and ectopic differentiation in the external germinal layer and molecular layer of the early postnatal cerebellum. We show that Bergmann glia in the cerebellum lose contact to the pial surface and have stunted processes. In vitro analysis revealed a depletion of Bergmann glia in the Jagged1 mutant mice. Our findings suggest that Jagged1 plays a role in cell fate specification and survival in the cerebellum.

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Citations

Jan 19, 2013·Molecular Neurobiology·Haiwei XuXiaotang Fan
Aug 29, 2013·Progress in Neurobiology·Annalisa Buffo, Ferdinando Rossi
Mar 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Domenico D'ArcaAnna Lasorella
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