Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Developmental cell death of cortical projection neurons is controlled by a Bcl11a/Bcl6-dependent pathway

ABSTRACT: Developmental neuron death plays a pivotal role in refining organization and wiring during neocortex formation. Aberrant regulation of this process results in neurodevelopmental disorders including impaired learning and memory. Underlying molecular pathways are incompletely determined. Loss of Bcl11a in cortical projection neurons induces pronounced cell death in upper-layer cortical projection neurons during postnatal corticogenesis. We use this genetic model to explore genetic mechanisms by which developmental neuron death is controlled. Unexpectedly, we find Bcl6, previously shown to be involved in transition of cortical neurons from progenitor to postmitotic differentiation state to provide a major check point regulating neuron survival during late cortical development. We show that Bcl11a is a direct transcriptional regulator of Bcl6. Deletion of Bcl6 exerts death of cortical projection neurons. In turn, reintroduction of Bcl6 into Bcl11a mutants prevents induction of cell death in these neurons. Together, our data identify a novel Bcl11a/Bcl6-dependent molecular pathway in regulation of developmental cell death during corticogenesis.

SUBMITTER: Christoph Wiegreffe

PROVIDER: S-SCDT-EMBOR-2021-54104V1 | biostudies-other |

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Developmental cell death of cortical projection neurons is controlled by a Bcl11a/Bcl6-dependent pathway.

Project description:Developmental neuron death plays a pivotal role in refining organization and wiring during neocortex formation. Aberrant regulation of this process results in neurodevelopmental disorders including impaired learning and memory. Underlying molecular pathways are incompletely determined. Loss of Bcl11a in cortical projection neurons induces pronounced cell death in upper-layer cortical projection neurons during postnatal corticogenesis. We use this genetic model to explore genetic mechanisms by which developmental neuron death is controlled. Unexpectedly, we find Bcl6, previously shown to be involved in the transition of cortical neurons from progenitor to postmitotic differentiation state to provide a major checkpoint regulating neuron survival during late cortical development. We show that Bcl11a is a direct transcriptional regulator of Bcl6. Deletion of Bcl6 exerts death of cortical projection neurons. In turn, reintroduction of Bcl6 into Bcl11a mutants prevents induction of cell death in these neurons. Together, our data identify a novel Bcl11a/Bcl6-dependent molecular pathway in regulation of developmental cell death during corticogenesis.

| S-EPMC9346488 | biostudies-literature

Developmental cell death of cortical projection neurons is controlled by a Bcl11a/Bcl6-dependent pathway II

Project description:Developmental neuron death plays a pivotal role in refining organization and wiring during neocortex formation. Aberrant regulation of this process results in neurodevelopmental disorders including impaired learning and memory. Underlying molecular pathways are incompletely determined. Loss of Bcl11a in cortical projection neurons induces pronounced cell death in upper-layer cortical projection neurons during postnatal corticogenesis. We used this genetic model to explore genetic mechanisms by which developmental neuron death is controlled. Unexpectedly, we found Bcl6, previously shown to be involved in transition of cortical neurons from progenitor to postmitotic differentiation state to provide a major check point regulating neuron survival during late cortical development. We show that Bcl11a is a direct transcriptional regulator of Bcl6. Deletion of Bcl6 exerts death of cortical projection neurons. In turn, reintroduction of Bcl6 into Bcl11a mutants prevents induction of cell death in these neurons. Together, our data identify a novel Bcl11a/Bcl6-dependent molecular pathway in regulation of developmental cell death during corticogenesis.

2022-06-24 | GSE185288 | GEO

Developmental cell death of cortical projection neurons is controlled by a Bcl11a/Bcl6-dependent pathway I

Project description:Developmental neuron death plays a pivotal role in refining organization and wiring during neocortex formation. Aberrant regulation of this process results in neurodevelopmental disorders including impaired learning and memory. Underlying molecular pathways are incompletely determined. Loss of Bcl11a in cortical projection neurons induces pronounced cell death in upper-layer cortical projection neurons during postnatal corticogenesis. We used this genetic model to explore genetic mechanisms by which developmental neuron death is controlled. Unexpectedly, we found Bcl6, previously shown to be involved in transition of cortical neurons from progenitor to postmitotic differentiation state to provide a major check point regulating neuron survival during late cortical development. We show that Bcl11a is a direct transcriptional regulator of Bcl6. Deletion of Bcl6 exerts death of cortical projection neurons. In turn, reintroduction of Bcl6 into Bcl11a mutants prevents induction of cell death in these neurons. Together, our data identify a novel Bcl11a/Bcl6-dependent molecular pathway in regulation of developmental cell death during corticogenesis.

2022-06-24 | GSE185287 | GEO

Developmental cell death of cortical projection neurons is controlled by a Bcl11a/Bcl6-dependent pathway I

Project description:Developmental cell death of cortical projection neurons is controlled by a Bcl11a/Bcl6-dependent pathway I

| PRJNA768459 | ENA

Developmental cell death of cortical projection neurons is controlled by a Bcl11a/Bcl6-dependent pathway II

Project description:Developmental cell death of cortical projection neurons is controlled by a Bcl11a/Bcl6-dependent pathway II

| PRJNA768460 | ENA

Bcl11a (Ctip1) controls migration of cortical projection neurons through regulation of Sema3c

Project description:During neocortical development, neurons undergo polarization, oriented migration, and layer type-specific differentiation. The transcriptional programs underlying these processes are not completely understood. Here we show that the transcription factor Bcl11a regulates polarity and migration of upper layer neurons. Bcl11a-deficient late-born neurons fail to correctly switch from multipolar to bipolar morphology resulting in impaired radial migration. We show that the expression of Sema3c is increased in migrating Bcl11a-deficient neurons and that Bcl11a is a direct negative regulator of Sema3c transcription. In vivo gain-of-function and rescue experiments demonstrate that Sema3c is a major downstream effector of Bcl11a required for the cell polarity switch and for the migration of upper layer neurons. Our data uncover a novel Bcl11a/Sema3c-dependent regulatory pathway used by migrating cortical neurons. Neocortex tissue from three control (Bcl11a+/+) and three Bcl11a mutants (Bcl11aΔflox/Δflox) embryos was collected at E14.5. Total RNA was isolated from each sample separately using the RNeasy kit (Qiagen). The isolated ENA was inspected for integrity and purity using an Agilent Bioanalyzer and a NanoDrop spectrophotometer, respectively. Microarray analyses were performed using 200 ng total RNA as starting material and 5.5 µg ssDNA per hybridization in a GeneChip Fluidics Station 450 (Affymetrix). The total RNAs were amplified and labeled following the Whole Transcript (WT) Sense Target Labeling Assay (Affymetrix). Labeled ssDNA was hybridized to Mouse Gene 1.0 ST Affymetrix GeneChip arrays (Affymetrix). The chips were scanned with a GeneChip Scanner 3000 (Affymetrix) and subsequent images analyzed using Affymetrix Expression Console Software (Affymetrix). A transcriptome analysis was performed using BRB-ArrayTools developed by Dr. Richard Simon and BRB-ArrayTools Development Team (http://linus.nci.nih.gov/BRB-ArrayTools.html).

2015-06-17 | E-GEOD-52827 | biostudies-arrayexpress

Transcription factors Bcl11a and Bcl11b are required for the production and differentiation of cortical projection neurons.

Project description:The generation and differentiation of cortical projection neurons are extensively regulated by interactive programs of transcriptional factors. Here, we report the cooperative functions of transcription factors Bcl11a and Bcl11b in regulating the development of cortical projection neurons. Among the cells derived from the cortical neural stem cells, Bcl11a is expressed in the progenitors and the projection neurons, while Bcl11b expression is restricted to the projection neurons. Using conditional knockout mice, we show that deficiency of Bcl11a leads to reduced proliferation and precocious differentiation of cortical progenitor cells, which is exacerbated when Bcl11b is simultaneously deleted. Besides defective neuronal production, the differentiation of cortical projection neurons is blocked in the absence of both Bcl11a and Bcl11b: Expression of both pan-cortical and subtype-specific genes is reduced or absent; axonal projections to the thalamus, hindbrain, spinal cord, and contralateral cortical hemisphere are reduced or absent. Furthermore, neurogenesis-to-gliogenesis switch is accelerated in the Bcl11a-CKO and Bcl11a/b-DCKO mice. Bcl11a likely regulates neurogenesis through repressing the Nr2f1 expression. These results demonstrate that Bcl11a and Bcl11b jointly play critical roles in the generation and differentiation of cortical projection neurons and in controlling the timing of neurogenesis-to-gliogenesis switch.

| S-EPMC9433425 | biostudies-literature

Bcl11a (Ctip1) controls migration of cortical projection neurons through regulation of Sema3c

2015-06-17 | GSE52827 | GEO

Loss of non-canonical KCC2 functions promotes developmental apoptosis of cortical projection neurons.

Project description:KCC2, encoded in humans by the SLC12A5 gene, is a multifunctional neuron-specific protein initially identified as the chloride (Cl- ) extruder critical for hyperpolarizing GABAA receptor currents. Independently of its canonical function as a K-Cl cotransporter, KCC2 regulates the actin cytoskeleton via molecular interactions mediated through its large intracellular C-terminal domain (CTD). Contrary to the common assumption that embryonic neocortical projection neurons express KCC2 at non-significant levels, here we show that loss of KCC2 enhances apoptosis of late-born upper-layer cortical projection neurons in the embryonic brain. In utero electroporation of plasmids encoding truncated, transport-dead KCC2 constructs retaining the CTD was as efficient as of that encoding full-length KCC2 in preventing elimination of migrating projection neurons upon conditional deletion of KCC2. This was in contrast to the effect of a full-length KCC2 construct bearing a CTD missense mutation (KCC2R952H ), which disrupts cytoskeletal interactions and has been found in patients with neurological and psychiatric disorders, notably seizures and epilepsy. Together, our findings indicate ion transport-independent, CTD-mediated regulation of developmental apoptosis by KCC2 in migrating cortical projection neurons.

| S-EPMC7132201 | biostudies-literature

Convergent cortical innervation of striatal projection neurons.

Project description:Anatomical studies have led to the assertion that intratelencephalic and pyramidal tract cortical neurons innervate different striatal projection neurons. To test this hypothesis, we measured the responses of mouse striatal neurons to optogenetic activation of intratelencephalic and pyramidal tract axons. Contrary to expectation, direct and indirect pathway striatal spiny projection neurons responded to both intratelencephalic and pyramidal tract activation, arguing that these cortical networks innervate both striatal projection neurons.

| S-EPMC4085670 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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