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Results report the identification of a novel long-range enhancer for Shh-Shh-brain-enhancer-6 (SBE6)-that is located 100 kb upstream of Shh and that is required for the proper induction of Shh expression during this differentiation program.
neuroectodermal Shh expression, dorsal/ventral patterning, and amount of proliferation in the ventral neuroectoderm was not changed in Wnt1 (zeige WNT1 Proteine)-Cre;Kif3a (zeige KIF3A Proteine)(fl/fl (zeige FLT3LG Proteine)) mutants; however, tissue polarity and directional cell division were disrupted.
The authors find that cholesterol, an important component of the cell membrane, directly binds to Smoothened and changes its shape so that it can activate Hedgehog signaling components inside cells.
Embryonal tumors with multilayered rosettes (ETMRs) are characterized by a parallel activation of Shh and Wnt (zeige WNT2 Proteine) signaling. Co-activation of these pathways in mouse neural precursors is sufficient to induce ETMR-like tumors in vivo that resemble their human counterparts on the basis of histology and global gene-expression analyses, and that point to apical radial glia cells as the possible tumor cell of origin.
reactivating SHH signaling in mutant lungs rescued the tip dilation phenotype and attenuated FGF signaling. Importantly, the reduced SHH signaling activity did not appear to be caused by decreased Shh expression or protein stability; instead, biologically active form of SHH proteins were reduced in both the Ext1 (zeige EXT1 Proteine) mutant epithelium and surrounding wild type mesenchymal cells.
provide compelling evidence that epidermal YAP (zeige YAP1 Proteine) and Hedgehog/GLI2 signalling undergo positive regulatory interactions in the control of normal epidermal homeostasis and in basal cell carcinoma (BCC) development, which in the large majority of cases is caused by aberrant Hedgehog signalling activity
conditional deletion of Shh in the anterior hypothalamus results in a fully penetrant phenotype characterised by a complete arrest of (Rathke's pouch) RP development, with lack of Lhx3 (zeige LHX3 Proteine)/Lhx4 (zeige LHX4 Proteine) expression in RP epithelium.
Shh production and Gli (zeige GLI1 Proteine) signaling is activated in vivo in lung, enhancing the Th2 response during a murine model of allergic asthma
Shh is in part responsible for the dependence of taste cell renewal on gustatory innervation, neurotrophic support of taste buds likely involves a complex set of factors.
GPC6 (zeige GPC6 Proteine) stimulates Hh signaling by binding to Hh and Ptc1 (zeige PTCH1 Proteine) at the cilium and increasing the interaction of the receptor and ligand to promote the growth of developing long bones.
Gorlin syndrome-derived induced pluripotent stem cells (iPSCs) expressed lower basal levels than control iPSCs of the genes encoding the Hh ligands Indian Hedgehog (IHH (zeige IHH Proteine)) and Sonic Hedgehog (SHH).
SHH activation is associated with Rhabdomyosarcoma.
Studies suggest that embryonic signaling pathways, the likes of Notch (zeige NOTCH1 Proteine), Wnt (zeige WNT2 Proteine), and Hedgehog and tumor marker Oct-4 (zeige POU5F1 Proteine) offer targets for cascade-specific molecular inhibition as they are fundamental to (cancer and normal) stem cell maintenance and growth.
Methylation at K436 and K595 respectively by Set7 (zeige SETD7 Proteine) increases the stability and DNA binding ability of Gli3 (zeige GLI3 Proteine), resulting in an enhancement of Shh signaling activation.
Altogether, these data suggested that curcumin inhibited the activities of BCSCs through suppressing Shh pathway, which might be an effective chemopreventive agent for bladder cancer intervention.
High SHH expression is associated with Small Cell Lung Cancer.
Accumulating evidence suggest that cytochrome P450 (CYP26 (zeige CYP26A1 Proteine)), the primary retinoid-inactivating enzyme, plays a critical role in the integration of two neoplastic molecular programs: the retinoid metabolism and Hedgehog pathways. (Review)
CHSY1 (zeige CHSY1 Proteine) overexpression in HCC (zeige FAM126A Proteine) contributes to the malignant behavior of hepatocellular carcinoma cells via activation of the hedgehog signaling pathway.
We found a novel 7q36.3 duplication involving 2 genes (SHH and RBM33) in a patient with complete corpus callosum agenesis (Figure), moderate learning difficulties, and macrocephaly
Study showed that SHH expression was significantly high among breast cancer patients with advanced tumor grade, stage, nodal involvement and metastasis and this expression strongly correlated with proliferation marker.
Data indicate that sonic hedgehog is expressed exclusively in the notochord but not in the spinal cord of the regenerate.
Dzip1 (zeige DZIP1 Proteine)-dependent stabilization of Spop (zeige SPOP Proteine)/HIB is evolutionarily conserved and essential for proper regulation of Gli (zeige GLI1 Proteine)/Ci proteins in the Hh pathway.
Notch (zeige NOTCH1 Proteine) 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 (zeige BMP4 Proteine) mRNA is up-regulated by sonic hedgehog.
In an examination of signaling pathways in developing Xenopus lung, shh but not ihh (zeige IHH Proteine) 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 (zeige DHCR7 Proteine) and Sonic Hedgehog are co-expressed during midline development in Xenopus embryos
study shows evolutionary alteration of a Ptch1 (zeige PTCH1 Proteine) cis (zeige CISH Proteine)-regulatory module, which no longer responds to graded SHH signalling during bovine handplate development
Mutation of hmgcs1 (zeige HMGCS1 Proteine) 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 (zeige GLI1 Proteine), a known Shh target gene, at 4 dpf, after morphological deficits in craniofacial development and chondrocyte differentiation were observed in hmgcs1 (zeige HMGCS1 Proteine) 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 (zeige MYLIP Proteine)-219 function accelerates the growth of primary cilia, revealing a possible mechanistic link between miR (zeige MYLIP Proteine)-219-mediated regulation of apical Par (zeige AFG3L2 Proteine) proteins and Shh signaling.
Shh is not essential for the early activation of has2 (zeige HAS2 Proteine), 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 (zeige SOX11 Proteine)-deficient zebrafish was caused by a large increase in shha transcription; indeed, suppressing Shha expression rescued the ocular phenotypes of sox11 (zeige SOX11 Proteine) morphants.
Pax6 (zeige PAX6 Proteine) has an evolutionarily conserved function in establishing the temporospatial expression of Shh in the mid-diencephalic organizer in vertebrates.
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 protein
, sonic hedgehog
, hemimelic extra toes
, short digits
, sonic hedgehog homolog
, sonic hedgehog protein A