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Bcl11b orchestrates subcerebral projection neuron axon development via cell-autonomous, non-cell-autonomous, and subcellular mechanisms

ABSTRACT: Bcl11b orchestrates subcerebral projection neuron axon development via cell-autonomous, non-cell-autonomous, and subcellular mechanisms

PROVIDER: PRJNA1082700 | ENA |

REPOSITORIES: ENA

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Bcl11b orchestrates subcerebral projection neuron axon development via cell-autonomous, non-cell-autonomous, and subcellular mechanisms

Project description:Both cell-intrinsic competency and extracellular cues regulate axon projection, but mechanisms that coordinate these elements remain poorly understood. Subcerebral projection neurons (SCPN) extend their primary axons from cortex through subcortical structures, including the striatum, targeting the brainstem and spinal cord. We identify that the transcription factor Bcl11b/Ctip2 functions in multiple independent neuron populations to control SCPN axon development. Bcl11b expressed by SCPN is required cell-autonomously for axonal outgrowth and efficient entry into the internal capsule within the striatum, while Bcl11b expressed by medium spiny neurons (MSN) non-cell-autonomously regulates SCPN axon fasciculation within the internal capsule and subsequent pathfinding. Further, integrated investigation of Bcl11b-null SCPN with transcriptomic, immunocytochemical, and in vivo growth cone purification approaches identifies that Cdh13 is localized along axons and on growth cone surfaces of SCPN in vivo, and mediates Bcl11b regulation of SCPN axonal outgrowth. Together, these results demonstrate that Bcl11b controls multiple aspects of SCPN axon development by coordinating intrinsic SCPN cell autonomous subcellular mechanisms and extrinsic MSN non-cell-autonomous mechanisms.

2025-01-09 | GSE260678 | GEO

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

Project description:Purpose:To assess changes in gene expression profiles of single cell from the wild type littermate controls cortices in E13.5, E15.5 and P0, and conditional knockout Bcl11a (and Bcl11b) at cortical projection neurons in the mouse cortices of the same ages. Methods: E13.5, E15.5 and P0 control and mutant cortices were carefully dissected under a clean environment. Then total RNA was isolated using an RNeasy Mini Kit (QIAGEN) according to the manufacturer’s protocol, quantified using NanoDrop ND-2000, and checked for RNA integrity using Agilent 2100 bioanalyzer. RNA-seq libraries were prepared according to the Illumina TruSeq protocol. Results: An average of 15 million reads per sample were obtained.

2021-08-31 | GSE182990 | GEO

BCL11B

Project description:BCL11B

| PRJNA330816 | ENA

Genome-wide identification of Bcl11b gene targets

Project description:B-cell leukemia/lymphoma 11B (Bcl11b) is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. Functional analysis on the gene target list identified significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. n=4 wt STHdh striatal cells and n=4 Bcl11b-transfected STHdh striatal cells

2011-08-01 | E-GEOD-31096 | biostudies-arrayexpress

Multiomic Analysis of Neurons with Divergent Projection Patterns Identifies Novel Regulators of Axon Pathfinding

Project description:Multiomic Analysis of Neurons with Divergent Projection Patterns Identifies Novel Regulators of Axon Pathfinding

| PRJNA763875 | ENA

Postnatal Conditional Knockout of Bcl11b in Striatal Projection Neurons Mimics the Transcriptional Signature of Huntington’s Disease

Project description:Dysregulation of the striatum is linked to multiple diseases including Huntington’s (HD), Parkinson’s, X-linked dystonia-parkinsonism (XDP), addiction, autism, and schizophrenia. Striatal medium spiny neurons (MSNs) make up 90% of the neuronal cell type in the striatum and are critical to motor control. The transcription factor Bcl11b (also known as CTIP2) is known to regulate of MSN differentiation, striatal striosome (patch) development and the architecture of the striatum during development. However, the function of Bcl11b adult striatal neurons in vivo has not been investigated. Therefore, we conditionally knocked out Bcl11b specifically in MSNs using D9-cre under the control of a regulatory elements of the mouse Ppp1r1b gene encoding DARPP-32 resulting in knockout around 5-6 weeks of age. Transcriptomic and behavioral analysis were performed on these mice.

2022-11-02 | GSE185476 | GEO

Mouse iNKT cell: Wild type Vs Bcl11b deficient

Project description:Transcriptional profiling of mouse iNKT cells comparing wild type and Bcl11b deficient cell. The mice were treated with 4 Î¼g of Î±-galactosylceramide. Goal was to determine the effects of transcription factor Bcl11b removal in iNKT cells. Intraperitoneal treatment with 4 Î¼g of Î±-Galactosylceramide. Two pair of wild type (BCL11b F/F VÎ±14 transgenic) and Knock out (BCL11b F/F PLZF-Cre VÎ±14 transgenic)) mice were treated. Lymphocytes from spleen and liver were enriched and stain with PBS-57 Loaded CD1d tetramer. Pure iNKT cells were collected through cell sorter.

2016-08-10 | E-GEOD-73679 | biostudies-arrayexpress

Expression profile of bcl11b-/- preselected DP thymocytes

Project description:Review on the role of Bcl11b in thymus and periphery and impact on diseases RNA was extracted from DP thymocytes of bcl11bf/fCd4cre/tcra-/- and tcra-/- mice. Tcra-/- mice only have preselected DP thymocytes. Such mice were used to determine the role of Bcl11b before selection, considering the defective positive selection in bcl11bf/fcd4cre mice. RNA was isolated and submitted for library generation and microarray analysis to determine expression profile of bcl11b-/- preselected DP thymocytes.

2014-04-12 | E-GEOD-56714 | biostudies-arrayexpress

Multiomic Analysis of Neurons with Divergent Projection Patterns Identifies Novel Regulators of Axon Pathfinding

Project description:Axon pathfinding is a key step during the formation of neural circuits but however the transcriptional mechanisms regulating its progression remain poorly understood. The binary decision of crossing or avoiding the midline that neurons make during developmente midline that mammalian retinal ganglion cell (RGC) axons take at the optic chiasm has classically represented a robust model to search for novel mechanisms controlling the selection of axonal trajectories. Here, in order to identify new axon pathfinding regulators, we compared the transcriptome and chromatin accessibility profiles of mammalian retinal ganglion cells RGCs projecting ipsilateral (iRGCs) or contralaterally (cRGCs). Overall, our analyses retrieved dozens of new molecules potentially involved in axon pathfinding and uncovered the regulatory logic behind axon trajectories selection.

2022-08-22 | GSE184275 | GEO

Postnatal Conditional Knockout of Bcl11b in Striatal Projection Neurons Mimics the Transcriptional Signature of Huntington’s Disease

Project description:Postnatal Conditional Knockout of Bcl11b in Striatal Projection Neurons Mimics the Transcriptional Signature of Huntington’s Disease

| PRJNA769140 | ENA

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