Pten coordinates retinal neurogenesis by regulating Notch signalling

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Development of nervous tissue is a coordinated process of neural progenitor cell (NPC) proliferation and neuronal differentiation. Intracellular signalling events that regulate the balance between NPC proliferation and neuronal differentiation, therefore, determine the size and composition of nervous tissues. Here, we demonstrate that negative regulation of phosphoinosite 3-kinase (PI3K)-Akt signalling by phosphatase tensin homologue (Pten) is essential for maintaining NPC population in mouse retina. We found that mouse retinal progenitor cells (RPCs) lacking the Pten gene complete neurogenesis earlier than their normal developmental schedule, resulting in their premature depletion in the mature retina. We further discover that Notch intracellular domain (NICD) fails to form transcription activator complex in Pten-deficient RPCs, and thereby unable to support RPC maintenance. Taken together, our results suggest that Pten plays a pivotal role in retinal neurogenesis by supporting Notch-driven RPC maintenance against neurogenic PI3K-Akt signalling. The EMBO Journal (2012) 31, 817-828. doi: 10.1038/emboj.2011.443; Published online 6 December 201 1
Publisher
NATURE PUBLISHING GROUP
Issue Date
2012-02
Language
English
Article Type
Article
Keywords

CELL-FATE DETERMINATION; PROTEIN-KINASE-C; VERTEBRATE RETINA; PROGENITOR CELLS; MOUSE RETINA; NEURAL REGENERATION; DOWN-REGULATION; GANGLION-CELLS; DIFFERENTIATION; PROLIFERATION

Citation

EMBO JOURNAL, v.31, no.4, pp.817 - 828

ISSN
0261-4189
DOI
10.1038/emboj.2011.443
URI
http://hdl.handle.net/10203/102219
Appears in Collection
BS-Journal Papers(저널논문)
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