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Publication : Rac-deficient cerebellar granule neurons die before they migrate to the internal granule layer.

First Author  Katayama KI Year  2022
Journal  Sci Rep Volume  12
Issue  1 Pages  14848
PubMed ID  36050459 Mgi Jnum  J:327991
Mgi Id  MGI:7334413 Doi  10.1038/s41598-022-19252-y
Citation  Katayama KI, et al. (2022) Rac-deficient cerebellar granule neurons die before they migrate to the internal granule layer. Sci Rep 12(1):14848
abstractText  Granule neurons are the most common cell type in the cerebellum. They are generated in the external granule layer and migrate inwardly, forming the internal granule layer. Small Rho GTPases play various roles during development of the nervous system and may be involved in generation, differentiation and migration of granule neurons. We deleted Rac1, a member of small Rho GTPases, by GFAP-Cre driver in cerebellar granule neurons and Bergmann glial cells. Rac1(flox/flox); Cre mice showed impaired migration and slight reduction in the number of granule neurons in the internal granule layer. Deletion of both Rac1 and Rac3 resulted in almost complete absence of granule neurons. Rac-deficient granule neurons differentiated into p27 and NeuN-expressing post mitotic neurons, but died before migration to the internal granule layer. Loss of Rac3 has little effect on granule neuron development. Rac1(flox/flox); Rac3(+/-); Cre mice showed intermediate phenotype between Rac1(flox/flox); Cre and Rac1(flox/flox); Rac3(-/-); Cre mice in both survival and migration of granule neurons. Rac3 itself seems to be unimportant in the development of the cerebellum, but has some roles in Rac1-deleted granule neurons. Conversely, overall morphology of Rac1(+/flox); Rac3(-/-); Cre cerebella was normal. One allele of Rac1 is therefore thought to be sufficient to promote development of cerebellar granule neurons.
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