A non-canonical role for the proneural gene
| Autor: | Sisu, Han, Daniel J, Dennis, Anjali, Balakrishnan, Rajiv, Dixit, Olivier, Britz, Dawn, Zinyk, Yacine, Touahri, Thomas, Olender, Marjorie, Brand, François, Guillemot, Deborah, Kurrasch, Carol, Schuurmans |
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| Rok vydání: | 2017 |
| Předmět: |
Neurons
Time Factors Transcription Genetic Neurogenesis Gene Expression Regulation Developmental Cell Differentiation Mice Transgenic Neocortex Nerve Tissue Proteins Embryo Mammalian Neural Stem Cells Neurogenins Proneural genes Basic Helix-Loop-Helix Transcription Factors Animals Cell Self Renewal Neuroglia Cell Proliferation Protein Binding Research Article bHLH transcription factors |
| Zdroj: | Development (Cambridge, England) |
| ISSN: | 1477-9129 |
| Popis: | Neural progenitors undergo temporal identity transitions to sequentially generate the neuronal and glial cells that make up the mature brain. Proneural genes have well-characterised roles in promoting neural cell differentiation and subtype specification, but they also regulate the timing of identity transitions through poorly understood mechanisms. Here, we investigated how the highly related proneural genes Neurog1 and Neurog2 interact to control the timing of neocortical neurogenesis. We found that Neurog1 acts in an atypical fashion as it is required to suppress rather than promote neuronal differentiation in early corticogenesis. In Neurog1−/− neocortices, early born neurons differentiate in excess, whereas, in vitro, Neurog1−/− progenitors have a decreased propensity to proliferate and form neurospheres. Instead, Neurog1−/− progenitors preferentially generate neurons, a phenotype restricted to the Neurog2+ progenitor pool. Mechanistically, Neurog1 and Neurog2 heterodimerise, and while Neurog1 and Neurog2 individually promote neurogenesis, misexpression together blocks this effect. Finally, Neurog1 is also required to induce the expression of neurogenic factors (Dll1 and Hes5) and to repress the expression of neuronal differentiation genes (Fezf2 and Neurod6). Neurog1 thus employs different mechanisms to temper the pace of early neocortical neurogenesis. Summary: Proneural genes are well known inducers of neurogenesis; however, Neurog1 induces the expression of Notch pathway genes and represses the expression of neuronal differentiation genes. |
| Databáze: | OpenAIRE |
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