ArticleGenes & development2010
A feedback loop mediated by degradation of an inhibitor is required to initiate neuronal differentiation.
Article in Genes & development, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
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- Cell-type specific global reprogramming of the transcriptome and epigenome in induced neurons with the 16p11.2 neuropsychiatric CNVs.European journal of human genetics : EJHG · 2025Article
- Old versus new: upstream and downstream of promyelocytic leukemia zinc finger protein.Cancer gene therapy · 2025Review
- The Cul3 ubiquitin ligase engages Insomniac as an adaptor to impact sleep and synaptic homeostasis.PLoS genetics · 2025Article
- Zbtb16 mediates a switch between Fgf signalling regimes in the developing hindbrain.Development (Cambridge, England) · 2023Article
- Expression Profile of New Marker Genes Involved in Differentiation of Human Wharton's Jelly-Derived Mesenchymal Stem Cells into Chondrocytes, Osteoblasts, Adipocytes and Neural-like Cells.International journal of molecular sciences · 2023Article
- Apoptosis Related Human Wharton's Jelly-Derived Stem Cells Differentiation into Osteoblasts, Chondrocytes, Adipocytes and Neural-like Cells-Complete Transcriptomic Assays.International journal of molecular sciences · 2023Article
- Segmentation and patterning of the vertebrate hindbrain.Development (Cambridge, England) · 2021Review
- Zbtb16 regulates social cognitive behaviors and neocortical development.Translational psychiatry · 2021Article
- Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells From Different Donors on Spinal Cord Injury in Mice.Frontiers in cellular neuroscience · 2021Article
- Genome sequencing of deep-sea hydrothermal vent snails reveals adaptions to extreme environments.GigaScience · 2020Article
- Control of craniofacial and brain development by Cullin3-RING ubiquitin ligases: Lessons from human disease genetics.Experimental cell research · 2020Review
- Synergic effects of aerobic exercise and eugenol supplement on germ cell development and testicular tissue structure in chlorpyrifos-treated animal model.Environmental science and pollution research international · 2020Article
- A single cell transcriptome atlas of the developing zebrafish hindbrain.Development (Cambridge, England) · 2020Article
- Shaping ofGenetics · 2019Article
- Promyelocytic leukemia zinc finger is involved in the formation of deep layer cortical neurons.Journal of biomedical science · 2019Article
- Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mammalian Cell Differentiation.Trends in biochemical sciences · 2018Review
- Role of PLZF as a tumor suppressor in prostate cancer.Oncotarget · 2017Review
- A non-canonical function of Ezh2 preserves immune homeostasis.EMBO reports · 2017Article
- KCTD2, an adaptor of Cullin3 E3 ubiquitin ligase, suppresses gliomagenesis by destabilizing c-Myc.Cell death and differentiation · 2017Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Neuronal differentiation is regulated by proneural genes that promote neurogenesis and inhibitory mechanisms that maintain progenitors. This raises the question of how the up-regulation of proneural genes required to initiate neurogenesis occurs in the presence of such inhibition. We carried out loss and gain of gene function, an interaction screen for binding partners, and biochemical analyses to uncover the regulation, developmental role, and mechanism of action of a ubiquitination adaptor protein, Btbd6a (BTB domain containing 6a). We find that the proneural gene neurog1 up-regulates btbd6a, which in turn is required for up-regulation of neurog1. Btbd6a is an adaptor for the Cul3 ubiquitin ligase complex, and we find that it binds to the transcriptional repressor Plzf (promyelocytic leukemia zinc finger). Btbd6a promotes the relocation of Plzf from nucleus to cytoplasm and targets Plzf for ubiquitination and degradation. plzfa is expressed widely in the neural epithelium; when overexpressed, it inhibits neurogenesis, and this inhibition is reversed by btbd6a. The antagonism of endogenous plzfa by btbd6a is required for neurogenesis, since the block in neuronal differentiation caused by btbd6a knockdown is alleviated by plzfa knockdown. These findings reveal a feedback loop mediated by degradation of an inhibitor that is essential for progenitors to undergo the transition to neuronal differentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.