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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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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

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

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

| PRJNA358040 | ENA

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.

2008-06-13 | E-GEOD-5582 | biostudies-arrayexpress

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. Keywords: neocortical astrocyte, cerebellar astrocyte, murine, postnatal day 1

2007-03-14 | GSE5582 | GEO

Neocortical Slices of Human Tissue

Project description:RNA-Seq data of human neocortical slices acute and after 7 and 14 days

2019-06-19 | GSE132954 | GEO

Genome wide analysis of chick limb bud tissue treated with FGF2 for 3hrs (RNA-Seq)

Project description:During limb development, in addition to proximal to distal outgrowth, FGF regulates a number of factors necessary for SHH expression. To elucidate the molecules involved in FGF-mediated SHH expression we implanted FGF2 beads in HH23 chicken forelimb buds and excised the SHH-expressing tissue for transcriptome analysis. The hypothesis is that this transcriptome data along with data from SHH-expressing tissue after a 24hr treatment would highlight molecules necessary for SHH FGF-mediated SHH expression. Results from the overlap provide a short-list of SHH-related genes which require further testing to assess their role in mediating SHH expression.

2018-12-18 | GSE114662 | GEO

Temporally defined neocortical translation and polysome assembly is determined by the RNA-binding protein, Hu antigen R

Project description:Precise spatiotemporal control of mRNA translation machinery is essential to proper development of highly complex systems like the neocortex. Here, we show that an RNA-binding protein, Hu antigen R (HuR), regulates both neocorticogenesis and specificity of neocortical translation machinery in a developmental stagedependent manner in mice. Neocortical absence of HuR alters the phosphorylation states of the initiation and elongation factors of the core translation machinery. In addition, HuR regulates the temporally specific positioning of functionally related mRNAs into the active translation sites, the polysomes. HuR also determines the specificity of neocortical polysomes by defining their combinatorial composition of ribosomal proteins and initiation and elongation factors. For some of the HuR-dependent proteins, the association with polysomes depends on the eIF2 alpha kinase 4 (eIF2ak4), which associated with HuR in prenatal developing neocortices. Finally, we found that deletion of HuR prior to embryonic day 10 (E10) disrupts both neocortical lamination and formation of the main neocortical commissure, the corpus callosum. Our study identifies a crucial role for HuR in neocortical development as a translational gatekeeper for functionally related mRNA subgroups and polysomal protein specificity. Cortex was dissected from mouse pups at embryonic day 13 (E13) or the day of birth (P0).

2014-08-25 | E-GEOD-50809 | biostudies-arrayexpress

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