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atomic insights into the recognition of the N-terminal domain of Sonic Hedgehog (HH-N) by PTCH1, offers a structural basis for cooperative binding of HH-N to various receptors and serves as a molecular framework for HH signalling and its malfunction in disease
3.5-angstrom resolution cryo-electron microscopy structure of native Sonic Hedgehog (SHH-N) in complex with PTCH1 at a physiological calcium concentration reconciles previous disparate findings and demonstrates that one SHH-N molecule engages both epitopes to bind two PTCH1 receptors in an asymmetric manner.
We did not detect any mutations in GLI3, SHH, or SHH ZRS in the 77 nonsyndromic polydactyly patients.
The elevated levels of both serum Shh and IL-6 were mainly observed in BC patients who had a significantly higher risk of early recurrence and bone metastasis, and associated with a worse survival for patients with progressive metastatic BC.
Disturbed SHH link between KIF7 and C5orf42 contributes to neurodevelopmental features characteristic of C5orf42-related ciliopathies.
Histone deacetylase 6 (HDAC6) inhibition enhanced glioma stem cells (GSCs) radiosensitivity via inactivating sonic hedgehog protein (SHH)/glioma-associated oncogene homolog 1 (Gli1) pathway.
Blockade of the Shh signaling pathway could reduce cell proliferation and migration only in MDA-MB-231 cells. Hh pathway inhibitor-1 (HPI-1) increased the percentages of late apoptotic cells in MDA-MB-231 cells and early apoptotic cells in T2 cells
Structure-guided mutational analysis shows that interaction between ShhN and Ptch1 is steroid-dependent.
Protease nexin-1 prevents growth of human B cell lymphoma via inhibition of sonic hedgehog signaling.
SHH-related signaling pathway affects antineoplastic drug resistance in cultured glioma cells.
SHH is expressed in cilia in the airway epithelial cells.SHH may mediate noncanonical hedgehog signaling through motile cilia to dampen respiratory defenses.
High SHH expression is associated with radioresistance in esophageal adenocarcinoma.
Identify SMO-dependent Shh signalling as a specific process for the activation of adventitial fibroblasts and the subsequent proliferation of smooth muscle cells and neointima formation.
In conclusion, our data suggest that overexpression of the Hedgehog components SHH, GLI2 and FOXA2 might be used as markers of an aggressive hemangioma.
These findings showed the upexpression of sonic hedgehog and vascular endothelial growth factor with co-localization in varicocele veins which imply that the reducing hypoxia or using sonic hedgehog antagonists may be helpful for this vascular disease.
Shh and Gli1 expression were associated with lymph node metastasis, TNM stage and tumor recurrence, suggesting Shh and Gli1 protein could become the valuable biomarker in evaluating the lymph node metastasis in oral squamous cell carcinoma.
Epithelial-mesenchymal transition programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling.
Case Report: medullablastoma with activated SHH expression.
NAFLD progression is usually accompanied by activation of the Sonic hedgehog (SHH) pathway leading to fibrous buildup (scar tissue) and inflammation of the liver tissue. For the first time patients with holoprosencephaly, a disease caused by SHH signaling mutations, are shown to have increased liver steatosis independent of obesity.
Gpr161 is a critical factor in the basal suppression machinery of Shh signaling, neural tube morphogenesis and closure. (Review)
Shh signal activation in Wnt active cells promotes the dermal papilla fate in scarring wounds.
quiescent dental stem cells are regulated by Shh signaling.
show that eliminating mouse MACS1 causes severe defects in laryngeal development, indicating that MACS1-directed Shh signalling is indispensable for respiratory organogenesis
Results suggest distinct functions of tuberous sclerosis complex 1 protein (Tsc1) and tuberous sclerosis complex 2 protein (Tsc2) in cellular signaling as the two genes affect ciliary length control and sonic hedgehog protein signaling via different mechanisms.
The results of this study indicated that Shh, Sfrp1, and Wnt5a collaborate to direct the pathfinding of descending 5-HT axons in the brainstem.
data illustrate that persistent Hh signaling in the palatal epithelium contributes to the etiology and pathogenesis of submucous cleft palate through its interaction with a p63/Irf6-dependent biological regulatory loop and through a p63-induced cell adhesion network.
SOX2 functions downstream of HH signaling to regulate lingual epithelium homeostasis.
High SHH expression is associated with medulloblastoma formation.
In the mutant Hammer toe (Hm) genome, a 150-kb noncoding DNA fragment from chromosome 14 is inserted into the region upstream of the Sonic hedgehog (Shh) promoter in chromosome 5. Two different regions are necessary for the syndactyly phenotype of Hm.
Data show that Sonic hedgehog (Shh), which encodes a secreted protein signal, is expressed in the sensory neurons, and that experimental ablation of neuronal Shh expression causes loss of taste receptor cells (TRCs).
Here by inducing expression of constitutively active Smoothened (SmoM2) or Gli2 (DeltaNGli2) in the adipocyte lineage of postnatal mice, the authors show that targeted activation of Hedgehog signaling suppresses high-fat-diet-induced obesity and improves whole-body glucose tolerance and insulin sensitivity.
These data suggest a potential novel mechanism in which alterations in SHH variance during evolution may have driven changes in limb patterning and digit length.
the knockdown of Ihh suppressed osteoblast growth and differentiation via a mechanism which may be associated with the TGF-beta/Smad and OPG/RANKL signaling pathways.
SHH signaling regulates the direction of cerebellar granule cells division.
The authors report here that Sonic Hedgehog (Shh)-Smoothened signaling downregulates Shisa2, which inhibits the glycosylation and cell surface presentation of Frizzled3 in rodent commissural axon growth cones.
ESP of fifth-stage larval Angiostrongylus cantonensis stimulates astrocyte activation and IL-1beta and IL-6 production through NF-kappaB and the Shh signaling pathway.
results indicate for the first time a possible mechanism involved in the crosstalk between fibroblasts and osteoblasts, as it was possible to observe trophic factors released by fibroblasts interfering decisively in osteoblast metabolism in a Shh-independent manner.
Importantly, Scube2 uncouples processing of Shh peptides from their lipid-mediated juxtamembrane positioning, and thereby explains the long-standing conundrum that N-terminally unlipidated Shh shows patterning activity in Scube2-expressing vertebrates
Mutation of hmgcs1 had no effect on Shh signaling at 2 and 3 days post fertilization (dpf), but did result in a decrease in the expression of gli1, a known Shh target gene, at 4 dpf, after morphological deficits in craniofacial development and chondrocyte differentiation were observed in hmgcs1 mutants.
Shha/Smo is functionally dedicated to ray branching during fin regeneration.
Shh and Rx3 govern formation of a distinct progenitor domain that elaborates patterning through its anisotropic growth and differentiation.
Time-lapse imaging revealed that knockdown of miR-219 function accelerates the growth of primary cilia, revealing a possible mechanistic link between miR-219-mediated regulation of apical Par proteins and Shh signaling.
Shh is not essential for the early activation of has2, but supports proper chondrogenic differentiation.
Opposing Shh and Fgf signals initiate nasotemporal patterning of the zebrafish retina.
Hedgehog signaling has a role in dental papilla formation and tooth size during zebrafish odontogenesis
Data indicate that the transgenic lines report Hedgehog pathway state in individual cells and with high sensitivity.
We further demonstrate that the elevated Hedgehog signaling in Sox11-deficient zebrafish was caused by a large increase in shha transcription; indeed, suppressing Shha expression rescued the ocular phenotypes of sox11 morphants.
Pax6 has an evolutionarily conserved function in establishing the temporospatial expression of Shh in the mid-diencephalic organizer in vertebrates.
Sulf1 triggers Shh signaling activity to establish and, later on, modify the spatial arrangement of gene expression in ventral neural progenitors
These studies provide evidence that a signaling pathway involving agrin, Fgfs and Shh may be a critical target of ethanol exposure during zebrafish embryogenesis.
heterozygote mutations in fgf8, shh or oep lead to a reduced number of ascending dopaminergic neurons in zebrafish and may confer increased susceptibility to the Parkinson disease
Hh is able to bypass VEGF to induce arterial differentiation in ECs via the calcitonin receptor-like receptor, thus revealing a surprising complexity in the interplay between Hh and VEGF signaling during arteriovenous specification.
analysis of Hh signaling which induces pancreatic fibrosis through paracrine activation of Hh-responsive cells in vivo
The present study investigates the role of the shha-expressing cells in the patterning of fin ray branches.
The Sphingosine-1-phospate-dependent anterior foregut endoderm functions primarily through Shh to regulate the growth but not dorsoventral patterning of zebrafish jaw precursors.
function for Bhmt involving modulation of Shh signaling to control beta-cell development.
Hedgehog and retinoic acid signaling cooperate to promote motoneurogenesis in zebrafish.
early Hh-signaling requirements in craniofacial development are indirect in Gli-dependent (Gli-d) transgenic line, Tg(Gli-d:mCherry) zebrafish
SHH-dependent E-ligase Midline1 regulates ubiquitin-mediated proteasomal degradation of Pax6 during visual system development.
Hh signaling is necessary and sufficient to initiate mouth formation, and Hh activation is required in a dose-dependent fashion to determine the size of the mouth
Data indicate that sonic hedgehog is expressed exclusively in the notochord but not in the spinal cord of the regenerate.
Dzip1-dependent stabilization of Spop/HIB is evolutionarily conserved and essential for proper regulation of Gli/Ci proteins in the Hh pathway.
Notch signaling promotes floor plate and hypochord fates over notochord, but has variable effects on Shh expression in the midline.
These results indicate that electrical activity and second-messenger signaling mediate Shh action in embryonic spinal neurons.
Connective tissue-specific expression of BMP-4 mRNA is up-regulated by sonic hedgehog.
In an examination of signaling pathways in developing Xenopus lung, shh but not ihh was expressed in the very anterior part of early lung epithelium.
Data propose that Shh serves as a ventral optic tract repellent that helps to define the caudal boundary for retinal axons in the diencephalon, and that this signaling is also required for initial target recognition at the optic tectum.
The forebrain of Xenopus revealed a largely conserved pattern of Shh expression among tetrapods.
Hedgehog regulates superficial slow muscle fibres in Xenopus and tetrapod trunk myogenesis
Results suggest that 7-dehydrocholesterol reductase and Sonic Hedgehog are co-expressed during midline development in Xenopus embryos
activated Hedgehog signaling in the blastema and found that target genes of Shh were inducible in the mesenchyme of limb blastema
study shows evolutionary alteration of a Ptch1 cis-regulatory module, which no longer responds to graded SHH signalling during bovine handplate development
Shh signaling pathway induces myopic development by activating MMP-2 in guinea pigs
This gene encodes a protein that is instrumental in patterning the early embryo. It has been implicated as the key inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites. Of three human proteins showing sequence and functional similarity to the sonic hedgehog protein of Drosophila, this protein is the most similar. The protein is made as a precursor that is autocatalytically cleaved\; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the developing embryo. Defects in this protein or in its signalling pathway are a cause of holoprosencephaly (HPE), a disorder in which the developing forebrain fails to correctly separate into right and left hemispheres. HPE is manifested by facial deformities. It is also thought that mutations in this gene or in its signalling pathway may be responsible for VACTERL syndrome, which is characterized by vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, cardiac anomalies, and limb abnormalities. Additionally, mutations in a long range enhancer located approximately 1 megabase upstream of this gene disrupt limb patterning and can result in preaxial polydactyly.
sonic hedgehog homolog
, sonic hedgehog protein
, hemimelic extra toes
, short digits
, sonic hedgehog protein A
, sonic hedgehog
, sonic hedgehog protein B
, tiggy winkle hedge hog
, tiggy winkle hedgehog
, tiggy-winkle hedgehog protein