ArticleNeural development2018
Genomic analysis of transcriptional networks directing progression of cell states during MGE development.
Article in Neural development, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 27 citations in OpenAlex.
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- Intraventricular haemorrhage in premature infants: the role of immature neuronal salt and water transport.Brain : a journal of neurology · 2024Article
- Defining cis-regulatory elements and transcription factors that control human cortical interneuron development.iScience · 2024Article
- Distinct requirements for Tcf3 and Tcf12 during oligodendrocyte development in the mouse telencephalon.Neural development · 2023Article
- Understanding and modeling regional specification of the human ganglionic eminence.Stem cell reports · 2023Article
- Hot topics in cellular neuropathology III: using CRISPR/Cas9 technology for deciphering central nervous system disease targets.Frontiers in cellular neuroscience · 2023Article
- DLX1 and the NuRD complex cooperate in enhancer decommissioning and transcriptional repression.Development (Cambridge, England) · 2022Article
- The Epigenome in Neurodevelopmental Disorders.Frontiers in neuroscience · 2021Review
- Transcriptional regulation of MGE progenitor proliferation by PRDM16 controls cortical GABAergic interneuron production.Development (Cambridge, England) · 2020Article
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- New Insights Into Cholinergic Neuron Diversity.Frontiers in molecular neuroscience · 2019Review
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundHomeodomain (HD) transcription factor (TF) NKX2-1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. NKX2-1 defines MGE regional identity in large part through transcriptional repression, while specification and maturation of GABAergic and cholinergic fates is mediated in part by transcriptional activation via TFs such as LHX6 and LHX8. Here we analyze the signaling and TF pathways, downstream of NKX2-1, required for GABAergic and cholinergic neuron fate maturation.
methodsDifferential ChIP-seq analysis was used to identify regulatory elements (REs) where chromatin state was sensitive to change in the Nkx2-1cKO MGE at embryonic day (E) 13.5. TF motifs in the REs were identified using RSAT. CRISPR-mediated genome editing was used to generate enhancer knockouts. Differential gene expression in these knockouts was analyzed through RT-qPCR and in situ hybridization. Functional analysis of motifs within hs623 was analyzed via site directed mutagenesis and reporter assays in primary MGE cultures.
resultsWe identified 4782 activating REs (aREs) and 6391 repressing REs (rREs) in the Nkx2-1 conditional knockout (Nkx2-1cKO) MGE. aREs are associated with basic-Helix-Loop-Helix (bHLH) TFs. Deletion of hs623, an intragenic Tcf12 aRE, caused a reduction of Tcf12 expression in the sub-ventricular zone (SVZ) and mantle zone (MZ) of the MGE. Mutation of LHX, SOX and octamers, within hs623, caused a reduction of hs623 activity in MGE primary cultures.
conclusionsTcf12 expression in the SVZ of the MGE is mediated through aRE hs623. The activity of hs623 is dependent on LHX6, SOX and octamers. Thus, maintaining the expression of Tcf12 in the SVZ involves on TF pathways parallel and genetically downstream of NKX2-1.
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