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SHH is downstream of immediate early genes and is targeted by chemotherapy on a specific enhancer [RNA-seq]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE183977 | GEO | 2021/12/31

REPOSITORIES: GEO

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SHH is downstream of immediate early genes and is targeted by chemotherapy on a specific enhancer [CUT&Tag, ATAC-seq]

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. The 139Kb upstream enhancer is specifically targeted by the immediate early gene EGR1.

2021-12-31 | GSE183663 | GEO

Development of a benzarone derivative as targeted therapy for SHH-medulloblastoma [Day 1]

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

Development of a benzarone derivative as targeted therapy for SHH-medulloblastoma [Day 5]

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Single cell RNA sequencing of mouse submandibular glands transferred with GFP or Shh gene

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.

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Olig2 targetome in SHH subgroup of medulloblastoma

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.

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Transcription profiling by array of rat cerebellar granular neuronal precursor cells plated with Sonic Hedgehog (Shh) and then treated with the PKA activator DBA

Project description:Cerebellar granular neuronal precursors were plated in presence of Sonic Hedgehog (Shh) for 24h and then treated with the PKA activator Dibutyryl Cyclic Adenosine Monophosphate (DBA) for addittional 24h

2008-07-11 | E-MEXP-1668 | biostudies-arrayexpress

Posterior Second Heart Field (pSHF) transcriptomes of wild-type and Shh mutant mouse embryos

2013-03-01 | GSE44754 | GEO

Posterior Second Heart Field (pSHF) transcriptomes of wild-type and Shh mutant mouse embryos

Project description:To understand Sonic hedgehog homolog (Shh)-mediated molecular networks in the posterior second heart field (pSHF), we have employed whole genome microarray expression profiling as a discovery platform to identify genes with Shh-dependent expressional changes. We microdissected the pSHF from E9.5 embryos and compared the Shh mutant samples with than of wild-type using Agilent 4x44k Mouse Whole Genome Arrays (n = 4 WT pools and 4 Shh - /- pools). Microdissected pSHF from E9.5 mouse embryos was molecularly verified by real-time PCR. Shh mutant embryos were compared with wild-type embryos. Four independnet pools of RNAs from each biological group were measured on 1-color Agilent Mouse Whole Genome Arrays (n = 3 WT pools and 4 Shh -/- pools).

2013-03-01 | E-GEOD-44754 | biostudies-arrayexpress

Expression data at 24 hours after the blocking of Shh signaling in tooth germs at embryonic day 14

Project description:The genetic mechanism governing the spatial patterning of teeth still remains to be elucidated. Sonic hedgehog (Shh) is one of key signaling molecules involved in the spatial patterning of teeth. By utilizing maternal transfer of 5E1 (an IgG1 monoclonal antibody against Shh protein) through the placenta to block Shh signaling, we investigated the changes in tooth patterning and in gene expression. We used microarrays to detect specific genes related with Shh signaling in tooth germs and identified some specific genes up- or down-regulated after blocking of Shh signaling activity.

2011-02-22 | GSE27429 | GEO

Polarized Dock Activity Drives Shh-Mediated Axon Guidance

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

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