ReviewFrontiers in molecular neuroscience2021
New Insights Into the Intricacies of Proneural Gene Regulation in the Embryonic and Adult Cerebral Cortex.
Review in Frontiers in molecular neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Direct neuronal reprogramming: emerging therapeutic strategies for neurodegenerative disorders.Annals of medicine · 2026Review
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- Conversion of human glial cells into neurons in ex vivo culture of human brain tissue: Essential roles of the transcription factors NeuroD1 and Ascl1.Neural regeneration research · 2026Article
- Integrating multi-omics data for next-generation cancer research and precision medicine.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- MCVAE-based multi-omic anomaly detection in Fragile X Syndrome.NAR molecular medicine · 2026Article
- Uncovering Hidden Phenotypes in NEX-Cre Mice: Behavioral and Cellular Alterations Demand Re-Evaluation of a Widely Used Transgenic Line.Journal of neurochemistry · 2026Article
- Identifying GFAP-expressing cell susceptibility to SARS-CoV-2 infection using human iPSC-derived neural cells.Scientific reports · 2026Article
- Neocortical neurogenesis: a proneural gene perspective.The FEBS journal · 2025Review
- The chemotherapy agent doxorubicin induces CNS expression of Ascl1, a regulator of adult neurogenesis and differentiation.Scientific reports · 2025Article
- Pharmacological inhibition of the Janus Kinases enhances ASCL1 protein stability and transcriptional activity.Molecular biology reports · 2025Article
- Examining the NEUROG2 lineage and associated gene expression in human cortical organoids.Development (Cambridge, England) · 2025Article
- Emerging Pro-neurogenic Therapeutic Strategies for Neurodegenerative Diseases: A Review of Pre-clinical and Clinical Research.Molecular neurobiology · 2025Review
- The Control of Cortical Folding: Multiple Mechanisms, Multiple Models.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- Recruitment of homodimeric proneural factors by conserved CAT-CAT E-boxes drives major epigenetic reconfiguration in cortical neurogenesis.Nucleic acids research · 2024Article
- Article
- Extramacrochaetae regulates Notch signaling in thebioRxiv : the preprint server for biology · 2024Article
- The Id protein Extramacrochaetae restrains the E protein Daughterless to regulate Notch, Rap1, and Sevenless within the R7 equivalence group of the Drosophila eye.Biology open · 2024Article
- Direct neuronal reprogramming of mouse astrocytes is associated with multiscale epigenome remodeling and requires Yy1.Nature neuroscience · 2024Article
- Long-Term Epigenetic Regulation ofInternational journal of molecular sciences · 2024Article
- Essential transcription factors for induced neuron differentiation.Nature communications · 2023Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Historically, the mammalian brain was thought to lack stem cells as no new neurons were found to be made in adulthood. That dogma changed ∼25 years ago with the identification of neural stem cells (NSCs) in the adult rodent forebrain. However, unlike rapidly self-renewing mature tissues (e.g., blood, intestinal crypts, skin), the majority of adult NSCs are quiescent, and those that become 'activated' are restricted to a few neurogenic zones that repopulate specific brain regions. Conversely, embryonic NSCs are actively proliferating and neurogenic. Investigations into the molecular control of the quiescence-to-proliferation-to-differentiation continuum in the embryonic and adult brain have identified proneural genes encoding basic-helix-loop-helix (bHLH) transcription factors (TFs) as critical regulators. These bHLH TFs initiate genetic programs that remove NSCs from quiescence and drive daughter neural progenitor cells (NPCs) to differentiate into specific neural cell subtypes, thereby contributing to the enormous cellular diversity of the adult brain. However, new insights have revealed that proneural gene activities are context-dependent and tightly regulated. Here we review how proneural bHLH TFs are regulated, with a focus on the murine cerebral cortex, drawing parallels where appropriate to other organisms and neural tissues. We discuss upstream regulatory events, post-translational modifications (phosphorylation, ubiquitinylation), protein-protein interactions, epigenetic and metabolic mechanisms that govern bHLH TF expression, stability, localization, and consequent transactivation of downstream target genes. These tight regulatory controls help to explain paradoxical findings of changes to bHLH activity in different cellular contexts.
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