Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex

ABSTRACT: Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9. Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2, were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5, an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons.

ORGANISM(S): Mus musculus

PROVIDER: GSE22371 | GEO | 2010/07/27

SECONDARY ACCESSION(S): PRJNA127649

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex

Project description:Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9. Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2, were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5, an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons. Mouse E14.5 neocortices and Postnatal day (P) 0.5 brains: E14.5 neocortices KO, 3; E14.5 neocortices WT, 3; Postnatal day (P) 0.5 brains frontal WT, 4; Postnatal day (P) 0.5 brains frontal KO, 4; Postnatal day (P) 0.5 brains parietal WT, 4; Postnatal day (P) 0.5 brains parietal KO, 4; Postnatal day (P) 0.5 brains occipital WT, 4; Postnatal day (P) 0.5 brains occipital KO, 4.

2010-07-27 | E-GEOD-22371 | biostudies-arrayexpress

Genome-wide distribution of Pbx1/2/3 in mouse cortex at embryonic day 12.5 [ChIP-seq]

Project description:We demonstrate using conditional mutagenesis that Pbx1, with and without Pbx2+/ sensitization, regulates regional identity and laminar patterning of the developing mouse neocortex in cortical progenitors (Emx1-Cre) and in newly generated neurons (Nex1-Cre). Pbx1/2 mutants have three salient molecular phenotypes of cortical regional and laminar organization: hypoplasia of the frontal cortex, ventral expansion of the dorsomedial cortex, and ventral expansion of Reelin expression in the cortical plate of the frontal cortex, concomitant with an inversion of cortical layering in the rostral cortex. Molecular analyses, including PBX ChIP-seq, provide evidence that PBX promotes frontal cortex identity by repressing genes that promote dorsocaudal fate. Chromatin immunoprecipitation was performed using antibody against Pbx1/2/3/ (sc-888, Santa Cruz). Wild type E12.5 mouse whole cortex was used for the analysis.

2016-02-27 | E-GEOD-78720 | biostudies-arrayexpress

Genome-wide distribution of Pbx1/2/3 in mouse cortex at embryonic day 15.5 [ChIP-seq]

Project description:We demonstrate using conditional mutagenesis that Pbx1, with and without Pbx2+/ sensitization, regulates regional identity and laminar patterning of the developing mouse neocortex in cortical progenitors (Emx1-Cre) and in newly generated neurons (Nex1-Cre). Pbx1/2 mutants have three salient molecular phenotypes of cortical regional and laminar organization: hypoplasia of the frontal cortex, ventral expansion of the dorsomedial cortex, and ventral expansion of Reelin expression in the cortical plate of the frontal cortex, concomitant with an inversion of cortical layering in the rostral cortex. Molecular analyses, including PBX ChIP-seq, provide evidence that PBX promotes frontal cortex identity by repressing genes that promote dorsocaudal fate. Chromatin immunoprecipitation was performed using antibody against Pbx1/2/3 (sc-888, Santa Cruz). Wild type E15.5 mouse whole cortex was used for the analysis.

2016-03-12 | E-GEOD-79152 | biostudies-arrayexpress

Genome-wide distribution of Pbx1/2/3 in mouse cortex at embryonic day 12.5 [ChIP-seq]

2016-02-27 | GSE78720 | GEO

Genome-wide distribution of Pbx1/2/3 in mouse cortex at embryonic day 15.5 [ChIP-seq]

2016-03-12 | GSE79152 | GEO

Mus musculus

Project description:Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex

| PRJNA127649 | ENA

The protomap is propagated to cortical plate neurons through an Eomes-dependent intermediate map

Project description:The cortical area map is initially patterned by transcription factor (TF) gradients in the neocortical primordium, which define a protomap in the embryonic ventricular zone (VZ). However, mechanisms that propagate regional identity from VZ progenitors to cortical plate (CP) neurons are unknown. Here we show that the VZ, subventricular zone (SVZ), and CP contain distinct molecular maps of regional identity, reflecting different gene expression gradients in radial glia progenitors, intermediate progenitors, and projection neurons, respectively. The intermediate map in SVZ is modulated by Eomes (also known as Tbr2), a T-box TF. Eomes inactivation caused rostrocaudal shifts in SVZ and CP gene expression, with loss of corticospinal axons and gain of corticotectal projections. These findings suggest that cortical areas and connections are shaped by sequential maps of regional identity, propagated by the Pax6 ? Eomes ? Tbr1 TF cascade. In humans, PAX6, EOMES, and TBR1 have been linked to intellectual disability and autism. To determine the role of Eomes in the propagation of the protomap to cortical plate neurons, used microarray analysis of E14.5 cortex from five wild type and three Eomes knockout mice.

2013-04-02 | E-GEOD-43387 | biostudies-arrayexpress

The Epigenetic Factor Landscape of Developing Neocortex is Regulated by Transcription Factors Pax6→Tbr2→Tbr1

Project description:Epigenetic factors (EFs) regulate multiple aspects of cerebral cortex development, including proliferation, neuronal differentiation, laminar fate, and regional identity. The same neurodevelopmental processes are also regulated by transcription factors (TFs), notably the Pax6→Tbr2→Tbr1 cascade expressed sequentially in radial glial progenitors, intermediate progenitors, and postmitotic projection neurons, respectively. Here, we studied the EF landscape and its regulation in embryonic mouse neocortex. Microarray and in situ hybridization assays revealed that many EF genes are expressed in specific cortical cell types, such as intermediate progenitors, or in rostrocaudal gradients. Furthermore, many EF genes are directly bound and transcriptionally regulated by Pax6, Tbr2, or Tbr1, as determined by chromatin immunoprecipitation-sequencing and gene expression analysis of TF mutant cortices. The results demonstrated that Pax6, Tbr2, and Tbr1 form a direct feedforward genetic cascade, with direct feedback repression. Results also revealed that each TF regulates multiple EF genes that control DNA methylation, histone marks, chromatin remodeling, and noncoding RNA.

2018-07-30 | GSE115703 | GEO

Analysis of TBR1 downnstream target genes in embryonic forebrains

Project description:TBR1 is a forebrain specific T-box transcription factor. Tbr1-/- mice have been characterized by defective axonal projections from cerebral cortex and abnormal neuronal migration of cerebral cortex and amygdala. To investigate how TBR1 regulates neural development, the gene expression profile of Tbr1-/- brains was compared with WT littermates. Total RNAs purified from forebrains at embryonic day 16.5 were hybridized on Affymetrix microarrays

2013-12-31 | E-GEOD-49237 | biostudies-arrayexpress

Analysis of TBR1 downnstream target genes in embryonic forebrains

2013-12-31 | GSE49237 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data