A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons
Open accessAbstract
Neurogenin1 (Ngn1), Neurogenin2(Ngn2), and Mash1 encode bHLH transcription factors with neuronal determination functions. In the telencephalon, the Ngns and Mash1 are expressed at high levels in complementary dorsal and ventral domains, respectively. We found that Ngn function is required to maintain these two separate expression domains, as Mash1 expression is up-regulated in the dorsal telencephalon of Ngn mutant embryos. We have taken advantage of the replacement of the Ngns by Mash1 in dorsal progenitors to address the role of the neural determination genes in neuronal-type specification in the telencephalon. In Ngn2 single and Ngn1; Ngn2 double mutants, a population of early born cortical neurons lose expression of dorsal-specific markers and ectopically express a subset of ventral telencephalic-specific markers. Analysis of Mash1; Ngn2 double mutant embryos and of embryos carrying a Ngn2 to Mash1 replacement mutation demonstrated that ectopic expression of Mash1 is required and sufficient to confer these ventral characteristics to cortical neurons. Our results indicate that in addition to acting as neuronal determinants, Mash1 and Ngns play a role in the specification of dorsal-ventral neuronal identity, directly linking pathways of neurogenesis and regional patterning in the forebrain.
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In the cell-type-specific networks, the authors found well-known transcription factors associated with brain development, including NEUROG1, DLGAP2, and MEF2A for excitatory neurons and GAD1, GAD2, and LHX6 for inhibitory neurons.
“In these, we found a number of well-known TFs associated with brain development—e.g., NEUROG1, DLGAP2, and MEF2A for excitatory neurons and GAD1, GAD2, and LHX6 for inhibitory neurons (Fig. 5G) (43–46).”
From Comprehensive functional genomic resource and integrative model for the human brain (2018) · cites this paper as [43]
Mef2c and Neurog1 stimulate neuronal differentiation.
“which have been reported to stimulate neuronal differentiation (Fode et al., 2000;Li et al., 2008; Fig. 7 F, H, J, L).”
From Comprehensive expression analyses of neural cell-type-specific miRNAs identify new determinants of the specification and maintenance of neuronal phenotypes (2013) · cites this paper as Fode et al., 2000
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- Authors
- Fode, C., Ma, Q., Casarosa, S., Ang, S.-L., Anderson, D. J., & Guillemot, F.
- Affiliations
- California Institute of Technology (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2000-01-01
- Volume
- 14
- Issue
- 1
- Pages
- 67-80
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC316337
- OpenAlex
- W2124109473
- Cited by
- 624
- References
- 80
- Citations by year
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- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Association pour la Recherche sur le Cancer
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- Medical Research Council Canada
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- neurogenin1, Neurogenin2, ASCL1, bHLH transcription factors, telencephalic neurons, cortical neurons, dorsoventral patterning, ectopic expression
- MeSH terms
- Base Sequence, DNA-Binding Proteins, Mutation, Nerve Tissue Proteins, Neurons, Telencephalon, Transcription Factors, Down-Regulation, DNA Primers, Gene Expression Regulation, Developmental, Cell Lineage, Basic Helix-Loop-Helix Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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