Mouse Brain SHH Pathway
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB46911 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR6474390.fastq.gz | Fastqsanger.gz | |||
| ERR6474400.fastq.gz | Fastqsanger.gz | |||
| ERR6474391.fastq.gz | Fastqsanger.gz | |||
| ERR6474401.fastq.gz | Fastqsanger.gz | |||
| ERR6474392.fastq.gz | Fastqsanger.gz |
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Project description:Before birth B-cells develop in the fetal liver (FL). Here we show that Gli3 activity in the FL stroma is required for B-cell development. In the Gli3-deficient FL B-cell development was reduced at multiple stages, whereas the Sonic hedgehog (Shh)-deficient FL showed increased B-cell development, and Gli3 functioned to repress Shh transcription. Use of a transgenic Hedgehog (Hh)-reporter mouse showed that Shh signals directly to developing B-cells, and that Hh pathway activation was increased in developing B-cells from Gli3-deficient fetal liver. RNAsequencing confirmed that Hh-mediated transcription is increased in B-lineage cells from Gli3-deficient FL, and showed that these cells expressed reduced levels of B-lineage transcription factors and BCR/pre-BCR-signalling genes. We showed that expression of the master regulators of B-cell development, Ebf1 and Pax5, is reduced in developing B-cells from Gli3-deficient FL and increased in Shh-deficient FL, and that in vitro Shh-treatment or neutralisation can repress or induce their expression respectively.
2017-05-09 | GSE81467 | GEO
Project description:The objective of this study was to identify genes regulated by Sonic Hedgehog pathway stimulation in neural progenitors. Paired (parallel culture) triplicates of neuralized embryoid body cultures with and without Shh pathway stimulation (Ag1.3-treatment)
2012-12-15 | E-GEOD-42565 | biostudies-arrayexpress
Project description:Sivakumar2011 - Hedgehog Signaling Pathway
This is the current model for the Hedgehog signaling pathway. The best data for mechanism of signaling has been worked out in Drosophila, so this model is based largely on Drosophila data. Hedgehog target genes vary from tissue to tissue, so the identities of individual target genes have not been listed. The main difference between the Drosophila and mammalian Hedgehog signaling pathways is the fact that there are three mammalian homologs of Cubitus interruptus, Gli1 Gli2 and Gli3. Some or all of the mammalian homologs may be proteolytically processed, but the data are controversial. There are two mammalian Ptc genes and three mammalian Hedgehog genes as well. The pathway for Sonic Hedgehog appears to be most similar to the Drosophila hedgehog pathway.
References:
Hedgehog signaling in animal development: paradigms and principles.
Sonic hedgehog in the nervous system: functions, modifications and mechanisms.
Hedgehog signal transduction: recent findings.
Hedgehog signaling: Costal-2 bridges the transduction gap.
This model is described in the article:
A systems biology approach to model neural stem cell regulation by notch, shh, wnt, and EGF signaling pathways.
Sivakumar KC, Dhanesh SB, Shobana S, James J, Mundayoor S.
Omics: a Journal of Integrative Biology. 2011; 15(10):729-737
Abstract:
The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have long been known to influence cell fate specification in the developing nervous system. Here we attempted to evaluate the contemporary knowledge about neural stem cell differentiation promoted by various drug-based regulations through a systems biology approach. Our model showed the phenomenon of DAPT-mediated antagonism of Enhancer of split [E(spl)] genes and enhancement of Shh target genes by a SAG agonist that were effectively demonstrated computationally and were consistent with experimental studies. However, in the case of model simulation of Wnt and EGF pathways, the model network did not supply any concurrent results with experimental data despite the fact that drugs were added at the appropriate positions. This paves insight into the potential of crosstalks between pathways considered in our study. Therefore, we manually developed a map of signaling crosstalk, which included the species connected by representatives from Notch, Shh, Wnt, and EGF pathways and highlighted the regulation of a single target gene, Hes-1, based on drug-induced simulations. These simulations provided results that matched with experimental studies. Therefore, these signaling crosstalk models complement as a tool toward the discovery of novel regulatory processes involved in neural stem cell maintenance, proliferation, and differentiation during mammalian central nervous system development. To our knowledge, this is the first report of a simple crosstalk map that highlights the differential regulation of neural stem cell differentiation and underscores the flow of positive and negative regulatory signals modulated by drugs.
This model is hosted on BioModels Database and identified by: BIOMD0000000395.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000395 | BioModels
Project description:Medulloblastoma is one of the most common malignant brain tumors of children, and 30% of medulloblastomas are driven by gain-of-function genetic lesions in the Sonic hedgehog (SHH) signaling pathway. Eyes Absent (EYA1), a haloacid dehalogenase (HAD) phosphatase and co-transcription factor, is critical for tumorigenesis and proliferation of SHH-medulloblastoma (SHH-MB). Benzarone and benzbromarone have been identified as allosteric inhibitors for the Eya proteins. Using benzarone as a point of departure, we developed a panel of 35 derivatives, and identified one new compound, DS-1-38, that functions as an Eya-antagonist, opposes SHH-signaling, inhibits SHH-MB growth in vitro and in vivo, shows excellent brain penetrance and increases the lifespan of mice predisposed to fatal SHH-MB. Our data suggest that DS-1-38 provides a path for developing targeted therapeutic for pediatric SHH-MB.
2023-12-21 | GSE229192 | GEO
Project description:Medulloblastoma is one of the most common malignant brain tumors of children, and 30% of medulloblastomas are driven by gain-of-function genetic lesions in the Sonic hedgehog (SHH) signaling pathway. Eyes Absent (EYA1), a haloacid dehalogenase (HAD) phosphatase and co-transcription factor, is critical for tumorigenesis and proliferation of SHH-medulloblastoma (SHH-MB). Benzarone and benzbromarone have been identified as allosteric inhibitors for the Eya proteins. Using benzarone as a point of departure, we developed a panel of 35 derivatives, and identified one new compound, DS-1-38, that functions as an Eya-antagonist, opposes SHH-signaling, inhibits SHH-MB growth in vitro and in vivo, shows excellent brain penetrance and increases the lifespan of mice predisposed to fatal SHH-MB. Our data suggest that DS-1-38 provides a path for developing targeted therapeutic for pediatric SHH-MB.
2023-12-21 | GSE229176 | GEO
Project description:Sonic Hedgehog (SHH) signaling is a key regulator of embryonic development and tissue homeostasis, and is involved in gastrointestinal (GI) cancer progression. Here we show that SHH gene expression is down-regulated by chemotherapy drugs.
2021-12-31 | GSE183977 | GEO
Project description:In the developing spinal cord, Sonic hedgehog (Shh) attracts commissural axons toward the floor plate. How Shh regulates the cytoskeletal remodeling that underlies growth cone turning is unknown. We found that Shh-mediated growth cone turning requires the activity of Docks, which are unconventional GEFs. Knockdown of Dock3 and 4, or their binding partner ELMO1 and 2, abolished commissural axon attraction by Shh in vitro. Dock3/4 and ELMO1/2 were also required for correct commissural axon guidance in vivo. Polarized Dock activity was sufficient to induce axon turning, indicating that Docks are instructive for axon guidance. Mechanistically, we show that Dock and ELMO interact with Boc, the Shh receptor, and that this interaction is reduced upon Shh stimulation. Furthermore, Shh stimulation translocates ELMO to the growth cone periphery and activates Rac1. This identifies Dock/ELMO as an effector complex of non-canonical Shh signaling and demonstrates the instructive role of GEFs in axon guidance.
2024-05-31 | GSE268644 | GEO
Project description:Several basic helix-loop-helix (bHLH) transcription factors are upregulated in Sonic Hedgehog subgroup of medulloblastoma (SHH MB). Olig2, a neural bHLH transcription factor known to regulate differentiation of neural cell populations, is broadly expressed in mouse models of SHH MB. ChIP-Seq of Olig2 revealed its binding to a large number of sites near genes known to promote SHH MB tumorigenesis, suggesting a potential role for Olig2 in regulating transcriptional programme of MB.
2024-03-23 | GSE103824 | GEO
Project description:To determine how Hedgehog signaling regulates salivary function, we performed single cell RNA sequencing (scRNA-seq) of adult mouse submandibular glands (SMGs) harvested 7 days after intra-SMG delivery of adenoviral vectors (Ad) carrying rat Sonic Hedgehog (Shh) or control GFP gene.
2023-04-10 | GSE148541 | GEO
Project description:Long non-coding RNAs (lncRNAs) comprise a diverse class of gene expression regulators with emerging roles in many biological processes including cancer. Here we show that the expression of the lncRNA Hedgehog Interacting Protein Antisense 1 (HHIP-AS1) is a hallmark feature of human SHH-driven tumors. Importantly, loss of HHIP-AS1 leads to reduced tumor growth in SHH-driven tumors in vitro and in vivo. Our results demonstrate the power of cross-entity transcriptome-wide comparisons to identify novel epigenetic–regulatory lncRNA circuitries underlying human cancers.
2022-06-01 | PXD016550 | Pride