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pmid: 15328020
Neurogenin (Ngn) 1 and Ngn2 encode basic-helix-loop-helix transcription factors expressed in the developing neocortex. Like other proneural genes, Ngns participate in the specification of neural fates and neuronal identities, but downstream effectors remain poorly defined. We set out to identify Ngn2 effectors in the cortex using a subtractive hybridization screen and identified several regionally expressed genes that were misregulated in Ngn2 and Ngn1; Ngn2 mutants. Included were genes down-regulated in germinal zone progenitors (e.g., Nlgn1, Unc5H4, and Dcc) and in postmitotic neurons in the cortical plate (e.g., Bhlhb5 and NFIB) and subplate (e.g., Mef2c, srGAP3, and protocadherin 9). Further analysis revealed that Ngn2 mutant subplate neurons were misspecified and that thalamocortical afferents (TCAs) that normally target this layer instead inappropriately projected towards the germinal zone. Strikingly, EphA5 and Sema3c, which encode repulsive guidance cues, were down-regulated in the Ngn2 and Ngn1; Ngn2 mutant germinal zones, providing a possible molecular basis for axonal targeting defects. Thus, we identified several new components of the differentiation cascade(s) activated downstream of Ngn1 and Ngn2 and provided novel insights into a new developmental process controlled by these proneural genes. Further analysis of the genes isolated in our screen should provide a fertile basis for understanding the molecular mechanisms underlying corticogenesis.
Genetic Markers, Models, Neurological, Mice, Transgenic, Neocortex, Nerve Tissue Proteins, Mice, axonal targeting, Basic Helix-Loop-Helix Transcription Factors, Animals, Molecular Biology, In Situ Hybridization, Body Patterning, Gene Library, Mice, Knockout, Neurons, thalamocortical, Gene Expression Regulation, Developmental, Cell Differentiation, Cell Biology, neocortex development, Axons, Mice, Mutant Strains, Neurogenin, downstream effectors, subplate, neuronal specification, Developmental Biology, Transcription Factors
Genetic Markers, Models, Neurological, Mice, Transgenic, Neocortex, Nerve Tissue Proteins, Mice, axonal targeting, Basic Helix-Loop-Helix Transcription Factors, Animals, Molecular Biology, In Situ Hybridization, Body Patterning, Gene Library, Mice, Knockout, Neurons, thalamocortical, Gene Expression Regulation, Developmental, Cell Differentiation, Cell Biology, neocortex development, Axons, Mice, Mutant Strains, Neurogenin, downstream effectors, subplate, neuronal specification, Developmental Biology, Transcription Factors
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 92 | |
popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Top 10% | |
influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Top 10% | |
impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 10% |