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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.
Mice, Knockout, Neurons, 571, Receptors, Notch, Transcription, Genetic, Neurogenesis, PTEN Phosphohydrolase, Immunohistochemistry, Retina, Cell Line, Mice, Phosphatidylinositol 3-Kinases, Animals, CELL-FATE DETERMINATION; PROTEIN-KINASE-C; VERTEBRATE RETINA; PROGENITOR CELLS; MOUSE RETINA; NEURAL REGENERATION; DOWN-REGULATION; GANGLION-CELLS; DIFFERENTIATION; PROLIFERATION, Proto-Oncogene Proteins c-akt, In Situ Hybridization, Signal Transduction
Mice, Knockout, Neurons, 571, Receptors, Notch, Transcription, Genetic, Neurogenesis, PTEN Phosphohydrolase, Immunohistochemistry, Retina, Cell Line, Mice, Phosphatidylinositol 3-Kinases, Animals, CELL-FATE DETERMINATION; PROTEIN-KINASE-C; VERTEBRATE RETINA; PROGENITOR CELLS; MOUSE RETINA; NEURAL REGENERATION; DOWN-REGULATION; GANGLION-CELLS; DIFFERENTIATION; PROLIFERATION, Proto-Oncogene Proteins c-akt, In Situ Hybridization, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 42 | |
popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Top 10% | |
influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Average | |
impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 10% |