Pten coordinates retinal neurogenesis by regulating Notch signalling
| Autor: | Jin Woo Kim, Cheol O. Joe, Kyung Hwa Kang, Hong Seok Jo |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
education.field_of_study
General Immunology and Microbiology biology General Neuroscience Neurogenesis Population Notch signaling pathway Cell fate determination General Biochemistry Genetics and Molecular Biology Cell biology biology.protein PTEN Tensin sense organs Progenitor cell education Molecular Biology PI3K/AKT/mTOR pathway |
| Zdroj: | The EMBO Journal. 31:817-828 |
| ISSN: | 0261-4189 |
| DOI: | 10.1038/emboj.2011.443 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text