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The Neocortical Progenitor Specification Program Is Established through Combined Modulation of SHH and FGF Signaling

ABSTRACT: The Neocortical Progenitor Specification Program Is Established through Combined Modulation of SHH and FGF Signaling

PROVIDER: PRJNA655828 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12407300.fastq.gz	Fastqsanger.gz
	SRR12407301.fastq.gz	Fastqsanger.gz
	SRR12407302.fastq.gz	Fastqsanger.gz
	SRR12407303.fastq.gz	Fastqsanger.gz
	SRR12407304.fastq.gz	Fastqsanger.gz

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The Neocortical Progenitor Specification Program Is Established through Combined Modulation of SHH and FGF Signaling.

Project description:Neuronal progenitors in the developing forebrain undergo dynamic competence states to ensure timely generation of specific excitatory and inhibitory neuronal subtypes from distinct neurogenic niches of the dorsal and ventral forebrain, respectively. Here we show evidence of progenitor plasticity when Sonic hedgehog (SHH) signaling is left unmodulated in the embryonic neocortex of the mammalian dorsal forebrain. We found that, at early stages of corticogenesis, loss of Suppressor of Fused (Sufu), a potent inhibitor of SHH signaling, in neocortical progenitors, altered the transcriptomic landscape of male mouse embryos. Ectopic activation of SHH signaling occurred, via degradation of Gli3R, resulting in significant upregulation of fibroblast growth factor 15 (FGF15) gene expression in all E12.5 Sufu-cKO neocortex regardless of sex. Consequently, activation of FGF signaling, and its downstream effector the MAPK signaling, facilitated expression of genes characteristic of ventral forebrain progenitors. Our studies identify the importance of modulating extrinsic niche signals such as SHH and FGF15, to maintain the competency and specification program of neocortical progenitors throughout corticogenesis.SIGNIFICANCE STATEMENT Low levels of FGF15 control progenitor proliferation and differentiation during neocortical development, but little is known on how FGF15 expression is maintained. Our studies identified SHH signaling as a critical activator of FGF15 expression during corticogenesis. We found that Sufu, via Gli3R, ensured low levels of FGF15 was expressed to prevent abnormal specification of neocortical progenitors. These studies advance our knowledge on the molecular mechanisms guiding the generation of specific neocortical neuronal lineages, their implications in neurodevelopmental diseases, and may guide future studies on how progenitor cells may be used for brain repair.

| S-EPMC7470916 | biostudies-literature

The Neocortical Progenitor Specification Program Is Established through Combined Modulation of SHH and FGF Signaling

Project description:Identification of gene expression changes in cortex-specific Sufu knockout mice

2020-08-08 | GSE155851 | GEO

Bulk RNA-seq of immunopanned astrocytes with the treatment of Shh and Fgf

Project description:Purpose: Examine differential gene expression changes in in vitro astrocytes with the administration of Shh agonist and Fgf protein vs control; Methods: Astrocytes were purified using a previously published immunopanning protocol, SAG-Shh agonist and DMSO are added into cell culture medium for 3 days, and Fgf2 and Fgf10 were added to medium respectively for 7 days, PBS treated astrocytes as controls. RNA-seq were perfomed (Lexongen QuantSeq3'mRNA-SEQ V2 Library prep kit) on all different conditions; Results: We observed differential gene expression changes in SAG treated conditions compared to WT, but did not observe a significant number of genes changes in Fgf treated groups compared to controls.

2025-04-13 | GSE281480 | GEO

Conserved transcriptional regulation by BRN1 and BRN2 in neocortical progenitors drives mammalian neural specification and neocortical expansion

Project description:Conserved transcriptional regulation by BRN1 and BRN2 in neocortical progenitors drives mammalian neural specification and neocortical expansion

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An Fgf-Shh signaling hierarchy regulates early specification of the zebrafish skull.

Project description:The neurocranium generates most of the craniofacial skeleton and consists of prechordal and postchordal regions. Although development of the prechordal is well studied, little is known of the postchordal region. Here we characterize a signaling hierarchy necessary for postchordal neurocranial development involving Fibroblast growth factor (Fgf) signaling for early specification of mesodermally-derived progenitor cells. The expression of hyaluron synthetase 2 (has2) in the cephalic mesoderm requires Fgf signaling and Has2 function, in turn, is required for postchordal neurocranial development. While Hedgehog (Hh)-deficient embryos also lack a postchordal neurocranium, this appears primarily due to a later defect in chondrocyte differentiation. Inhibitor studies demonstrate that postchordal neurocranial development requires early Fgf and later Hh signaling. Collectively, our results provide a mechanistic understanding of early postchordal neurocranial development and demonstrate a hierarchy of signaling between Fgf and Hh in the development of this structure.

| S-EPMC4967541 | biostudies-literature

Bulk RNA-seq of immunopanned astrocytes with the treatment of Shh and Fgf

Project description:Bulk RNA-seq of immunopanned astrocytes with the treatment of Shh and Fgf

| PRJNA1184114 | ENA

Conserved transcriptional regulation by BRN1 and BRN2 in neocortical progenitors drives mammalian neural specification and neocortical expansion

Project description:To investigate BRN1/2 function in neocortical development, we knockout BRN1/2 in the dorsal telencephalon (BRN1/2 cKO) We then performed gene expression profiling analysis using data obtained from scRNA-seq of 13 different mice at E12.5 and E14.5

2024-07-05 | GSE229129 | GEO

Integration of Shh and Fgf signaling in controlling Hox expression in cultured limb cells

Project description:Integration of Shh and Fgf signaling in controlling Hox expression in cultured limb cells

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Gene Expression Changes in Definitive Endoderm in response to FGF Signaling

Project description:FGF Signaling is required for hepatic progenitor cell formation from endoderm. The mechanism of this process is poorly understood We used microarrays to identify genes directly regulated by FGF signaling in definitive endoderm that may be involved in hepatic specification.

2015-12-01 | GSE69533 | GEO

Transcription profiling of mouse neocortical and cerebellar astrocytes

Project description:Affymetrix Mouse Genome 430 2.0 GeneChip microarrays were used to analyze murine neocortical and cerbellar astrocytes generated from postnatal (PN) day 1 wild-type (ICR) pups. Experiment Overall Design: Three samples each of murine neocortical and cerebellar astrocytes were analyzed.

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