Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA230251 | ENA |
REPOSITORIES: ENA
Similar Datasets
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
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
Project description:Completion of neuronal migration is critical for brain development. Kif21b is a plus-end directed kinesin motor protein that promotes intracellular transport and controls microtubule dynamics in neurons. Here we report a physiological function of Kif21b during radial migration of projection neurons in the mouse developing cortex. In vivo analysis in mouse and live imaging on cultured slices demonstrate that Kif21b regulates the radial glia-guided locomotion of new-born neurons independently of its motility on microtubules. Unexpectedly we show that Kif21b directly binds and regulates the actin cytoskeleton both in vitro and in vivo in migratory neurons. We establish that Kif21b-mediated regulation of actin cytoskeleton dynamics influences branching and nucleokinesis during neuronal locomotion. Altogether, our results reveal atypical roles of Kif21b on the actin cytoskeleton during migration of cortical projection neurons
2023-07-04 | PXD042855 | Pride
Project description:Interneurons navigate along multiple tangential paths to settle into appropriate cortical layer. They undergo saltatory migration, which is paced by intermittent nuclear jumps whose regulation relies on interplay between extracellular cues and genetic-encoded information. However, it remains unclear how cycles of pause and movement are coordinated at the molecular level. Post-translational modification of proteins contributes to cell migration regulation. The present study uncovers that carboxypeptidase 1, which promotes deglutamylation, is a pivotal regulator of pausing of cortical interneurons. Moreover, we show that pausing during migration controls the flow of interneurons invading the cortex by generating heterogeinity in movement at the population level. Interfering with the regulation of pausing not only affects the size of the cortical interneuron cohort but also secondarily impairs the generation of age-matched upper layer projection neurons.
2018-02-14 | PXD006397 | Pride
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.
2015-06-17 | GSE52827 | GEO
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
Project description:Transcription factor 4 controls positioning of cortical projection neurons through regulation of cell adhesion
| PRJNA700842 | ENA
Project description:Identification of molecular controls of Corticothalamic projection neurons differentiatiion
| PRJNA261937 | ENA
Project description:TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons
| PRJNA338690 | ENA