ArticleNeural development2014
E-proteins orchestrate the progression of neural stem cell differentiation in the postnatal forebrain.
Article in Neural development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
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- Defining the spatial-molecular map of fibrotic tendon healing and the drivers of Scleraxis-lineage cell fate and function.Cell reports · 2022Article
- Comparative parallel multi-omics analysis during the induction of pluripotent and trophectoderm states.Nature communications · 2022Article
- Transcription Factor 4 loss-of-function is associated with deficits in progenitor proliferation and cortical neuron content.Nature communications · 2022Article
- Tcf12 and NeuroD1 cooperatively drive neuronal migration during cortical development.Development (Cambridge, England) · 2022Article
- Expression of alternative transcription factor 4 mRNAs and protein isoforms in the developing and adult rodent and human tissues.Frontiers in molecular neuroscience · 2022Article
- Lipid droplet availability affects neural stem/progenitor cell metabolism and proliferation.Nature communications · 2021Article
- Functional consequences of TCF4 missense substitutions associated with Pitt-Hopkins syndrome, mild intellectual disability, and schizophrenia.The Journal of biological chemistry · 2021Article
- Homodimeric and Heterodimeric Interactions among Vertebrate Basic Helix-Loop-Helix Transcription Factors.International journal of molecular sciences · 2021Review
- Adult neural stem cells have latent inflammatory potential that is kept suppressed byScience advances · 2021Article
- Article
- Transcription factor 4 and its association with psychiatric disorders.Translational psychiatry · 2021Review
- Cypermethrin Impairs Hippocampal Neurogenesis and Cognitive Functions by Altering Neural Fate Decisions in the Rat Brain.Molecular neurobiology · 2021Article
- E2A regulates neural ectoderm fate specification in human embryonic stem cells.Development (Cambridge, England) · 2020Article
- Enriched environment ameliorates adult hippocampal neurogenesis deficits in Tcf4 haploinsufficient mice.BMC neuroscience · 2020Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeural stem cell (NSC) differentiation is a complex multistep process that persists in specific regions of the postnatal forebrain and requires tight regulation throughout life. The transcriptional control of NSC proliferation and specification involves Class II (proneural) and Class V (Id1-4) basic helix-loop-helix (bHLH) proteins. In this study, we analyzed the pattern of expression of their dimerization partners, Class I bHLH proteins (E-proteins), and explored their putative role in orchestrating postnatal subventricular zone (SVZ) neurogenesis.
resultsOverexpression of a dominant-negative form of the E-protein E47 (dnE47) confirmed a crucial role for bHLH transcriptional networks in postnatal neurogenesis by dramatically blocking SVZ NSC differentiation. In situ hybridization was used in combination with RT-qPCR to measure and compare the level of expression of E-protein transcripts (E2-2, E2A, and HEB) in the neonatal and adult SVZ as well as in magnetic affinity cell sorted progenitor cells and neuroblasts. Our results evidence that E-protein transcripts, in particular E2-2 and E2A, are enriched in the postnatal SVZ with expression levels increasing as cells engage towards neuronal differentiation. To investigate the role of E-proteins in orchestrating lineage progression, both in vitro and in vivo gain-of-function and loss-of-function experiments were performed for individual E-proteins. Overexpression of E2-2 and E2A promoted SVZ neurogenesis by enhancing not only radial glial cell differentiation but also cell cycle exit of their progeny. Conversely, knock-down by shRNA electroporation resulted in opposite effects. Manipulation of E-proteins and/or Ascl1 in SVZ NSC cultures indicated that those effects were Ascl1 dependent, although they could not solely be attributed to an Ascl1-induced switch from promoting cell proliferation to triggering cell cycle arrest and differentiation.
conclusionsIn contrast to former concepts, suggesting ubiquitous expression and subsidiary function for E-proteins to foster postnatal neurogenesis, this work unveils E-proteins as being active players in the orchestration of postnatal SVZ neurogenesis.
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