Pten coordinates retinal neurogenesis by regulating Notch signalling

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 nervou...

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Bibliographic Details
Published in:The EMBO journal 2012-02, Vol.31 (4), p.817-828
Main Authors: Jo, Hong Seok, Kang, Kyung Hwa, Joe, Cheol O, Kim, Jin Woo
Format: Article
Language:English
Subjects:
Akt
Animals
Cell growth
Cell Line
EMBO27
EMBO37
Gene expression
Immunohistochemistry
In Situ Hybridization
Mice
Mice, Knockout
Molecular biology
Nervous tissues
Neurogenesis - physiology
Neurons
Neurons - cytology
Neurons - metabolism
notch signalling
phosphatase tensin homologue (PTEN)
Phosphatidylinositol 3-Kinases - metabolism
Proteins
Proto-Oncogene Proteins c-akt - metabolism
PTEN Phosphohydrolase - physiology
Receptors, Notch - metabolism
Retina - cytology
retinal neurogenesis
retinal progenitor cell (RPC)
Signal Transduction
Transcription, Genetic
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Summary: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. Mouse retinal progenitor cells lacking the phosphatase Pten complete neurogenesis prematurely due to inactivation of Notch signalling. Loss of Pten leads to enhanced PI3K‐Akt signalling that interferes with the formation of Notch transcription activator complex.
ISSN:0261-4189
1460-2075
DOI:10.1038/emboj.2011.443