Transient inactivation of Notch signaling synchronizes differentiation of neural progenitor cells
| Autor: | Sean Georgi, Byron H. Hartman, Branden R. Nelson, Thomas A. Reh, Michael S. Lan |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
HES5
Notch signaling pathway Chick Embryo Biology Retina Article 03 medical and health sciences 0302 clinical medicine Basic Helix-Loop-Helix Transcription Factors Animals Proneural bHLH transcription factor HES1 Progenitor cell Molecular Biology Triglycerides gamma-Aminobutyric Acid 030304 developmental biology Progenitor Oligonucleotide Array Sequence Analysis Neurons 0303 health sciences Receptors Notch Stem Cells Gene Expression Regulation Developmental Cell Differentiation Cell Biology Molecular biology Insulinoma-associated 1 Neural stem cell Cell biology Hes1 Notch proteins Hes3 signaling axis Notch activity Amyloid Precursor Protein Secretases Neural differentiation Hes5 Neuroglia 030217 neurology & neurosurgery Signal Transduction Developmental Biology |
| Zdroj: | Developmental Biology. 304(2):479-498 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2007.01.001 |
| Popis: | In the developing nervous system, the balance between proliferation and differentiation is critical to generate the appropriate numbers and types of neurons and glia. Notch signaling maintains the progenitor pool throughout this process. While many components of the Notch pathway have been identified, the downstream molecular events leading to neural differentiation are not well understood. We have taken advantage of a small molecule inhibitor, DAPT, to block Notch activity in retinal progenitor cells, and analyzed the resulting molecular and cellular changes over time. DAPT treatment causes a massive, coordinated differentiation of progenitors that produces cell types appropriate for their developmental stage. Transient exposure of retina to DAPT for specific time periods allowed us to define the period of Notch inactivation that is required for a permanent commitment to differentiate. Inactivation of Notch signaling revealed a cascade of proneural bHLH transcription factor gene expression that correlates with stages in progenitor cell differentiation. Microarray/QPCR analysis confirms the changes in Notch signaling components, and reveals new molecular targets for investigating neuronal differentiation. Thus, transient inactivation of Notch signaling synchronizes progenitor cell differentiation, and allows for a systematic analysis of key steps in this process. |
| Databáze: | OpenAIRE |
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