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of outstanding interest. Reports the isolation of the first homologue of Drosophila patched from a vertebrate species; analysis of the spatial pattern of expression suggests the regulatory relationship between PTC and HH signalling has been conserved in evolution, an inference supported by the finding that ectopic Shh induces PTC transcription.
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Goodrich LV, Johnson RL, Milenkovic L, McMahon JA, Scott MP. Conservation of the hedgehog/patched signaling pathway from flies to mice - induction of a mouse patched gene by hedgehog. of outstanding interest Genes Dev. 10:1996;301-312 Reports the isolation of the first homologue of Drosophila patched from a vertebrate species; analysis of the spatial pattern of expression suggests the regulatory relationship between PTC and HH signalling has been conserved in evolution, an inference supported by the finding that ectopic Shh induces PTC transcription.
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Goodrich, L.V.1
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Scott, M.P.5
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of special interest. The authors describe the cloning and expression analysis of a homologue of ptc in the chick; using virally mediated misexpression of Shh, they confirm that Shh regulates ptc transcription in vertebrates. In addition, the expression pattern of Ptc around the cartilage condensations in the chick limb suggest that another member of the signalling family, Indian hedgehog, also regulates Ptc transcription. The independence of Ptc transcription of fibroblast growth factor signals from the ectoderm suggests that Ptc is a direct target of Shh activity.
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Marigo V, Scott MP, Johnson RL, Goodrich LV, Tabin CJ. Conservation in hedgehog signaling: induction of a chicken patched homolog by Sonic hedgehog in the developing limb. of special interest Development. 122:1996;1225-1233 The authors describe the cloning and expression analysis of a homologue of ptc in the chick; using virally mediated misexpression of Shh, they confirm that Shh regulates ptc transcription in vertebrates. In addition, the expression pattern of Ptc around the cartilage condensations in the chick limb suggest that another member of the signalling family, Indian hedgehog, also regulates Ptc transcription. The independence of Ptc transcription of fibroblast growth factor signals from the ectoderm suggests that Ptc is a direct target of Shh activity.
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Development
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Marigo, V.1
Scott, M.P.2
Johnson, R.L.3
Goodrich, L.V.4
Tabin, C.J.5
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0029791854
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Spatial regulation of a Zebrafish patched Homologue reflects the roles of sonic hedgehog and Protein Kinase A in neural tube and somite patterning
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of special interest. PCR amplification identifies two ptc-related genes in the zebrafish. Expression of one of these is very similar to that reported for mouse and chick and can be induced both by ectopic Shh expression and, like Drosophila ptc, by blocking protein kinase A.
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Concordet J-P, Lewis K, Moore J, Goodrich LV, Johnson RL, Scott MP, Ingham PW. Spatial regulation of a Zebrafish patched Homologue reflects the roles of sonic hedgehog and Protein Kinase A in neural tube and somite patterning. of special interest Development. 122:1996;2835-2846 PCR amplification identifies two ptc-related genes in the zebrafish. Expression of one of these is very similar to that reported for mouse and chick and can be induced both by ectopic Shh expression and, like Drosophila ptc, by blocking protein kinase A.
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Development
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Concordet J-P1
Lewis, K.2
Moore, J.3
Goodrich, L.V.4
Johnson, R.L.5
Scott, M.P.6
Ingham, P.W.7
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A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities
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of special interest. Characterisation of ptc homologues from mouse and human indicates that in mouse Ptc is expressed adjacent to Shh-expressing tissues and that in humans Ptc maps to the locus mutated in nevoid basal cell carcinoma (Gorlin's) syndrome.
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Hahn H, Christiansen J, Wicking C, Zaphiropoulos PG, Chidambaram A, Gerrard B, Vorechovsky I, Bale AE, Toftgard R, Dean M, Wainwright B. A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities. of special interest J Biol Chem. 271:1996;12125-12128 Characterisation of ptc homologues from mouse and human indicates that in mouse Ptc is expressed adjacent to Shh-expressing tissues and that in humans Ptc maps to the locus mutated in nevoid basal cell carcinoma (Gorlin's) syndrome.
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J Biol Chem
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Hahn, H.1
Christiansen, J.2
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Gerrard, B.6
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Human homolog of patched, a candidate gene for the basal-cell nevus syndrome
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of outstanding interest. The cloning of the human homologue of Ptc led to the identification of germline mutations in this gene in patients with Gorlin's syndrome, suggesting that haploinsufficiency of Ptc results in the developmental defects seen in Gorlin's patients. In addition, the discovery of somatic mutations in the second Ptc allele in BCCs from Gorlin's patients strongly suggests that Ptc is a tumour suppressor gene responsible for BCC, a view reinforced by the discovery of Ptc mutations in spontaneous BCCs.
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Johnson RL, Rothman AL, Xie JW, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH, Scott MP. Human homolog of patched, a candidate gene for the basal-cell nevus syndrome. of outstanding interest Science. 272:1996;1668-1671 The cloning of the human homologue of Ptc led to the identification of germline mutations in this gene in patients with Gorlin's syndrome, suggesting that haploinsufficiency of Ptc results in the developmental defects seen in Gorlin's patients. In addition, the discovery of somatic mutations in the second Ptc allele in BCCs from Gorlin's patients strongly suggests that Ptc is a tumour suppressor gene responsible for BCC, a view reinforced by the discovery of Ptc mutations in spontaneous BCCs.
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Science
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Johnson, R.L.1
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Scott, M.P.11
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13
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Mutations of the human homolog of Drosophila patched in the nevoid basal-cell carcinoma syndrome
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of outstanding interest. Positional cloning of the region implicated in Gorlin's syndrome, 9q22, and the identification of cosmids that detect RFLPs by pulse field gel electrophoresis leads to the identification of human Ptc as a candidate gene for the syndrome. BCCs from two patients carry mutations in single Ptc alleles.
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Hahn H, Wicking C, Zaphiropoulos PG, Gailani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, et al. Mutations of the human homolog of Drosophila patched in the nevoid basal-cell carcinoma syndrome. of outstanding interest Cell. 85:1996;841-851 Positional cloning of the region implicated in Gorlin's syndrome, 9q22, and the identification of cosmids that detect RFLPs by pulse field gel electrophoresis leads to the identification of human Ptc as a candidate gene for the syndrome. BCCs from two patients carry mutations in single Ptc alleles.
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Cell
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Hahn, H.1
Wicking, C.2
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Biochemical-evidence that Patched is the Hedgehog receptor
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of outstanding interest. Xenopus oocytes expressing chicken Ptc protein bind iodinated N-Shh protein with high affinity. Shh could be outcompeted with excess unlabelled Shh protein or with a function-blocking antibody, demonstrating specificity of the interaction; in addition, deletions of the extracellular domains of Ptc were found to completely abolish Shh binding.
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Marigo V, Davey R, Zuo Y, Cunningham J, Tabin C. Biochemical-evidence that Patched is the Hedgehog receptor. of outstanding interest Nature. 384:1996;176-179 Xenopus oocytes expressing chicken Ptc protein bind iodinated N-Shh protein with high affinity. Shh could be outcompeted with excess unlabelled Shh protein or with a function-blocking antibody, demonstrating specificity of the interaction; in addition, deletions of the extracellular domains of Ptc were found to completely abolish Shh binding.
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Nature
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Marigo, V.1
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The tumor-suppressor gene patched encodes a candidate receptor for Sonic hedgehog
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of outstanding interest. Description of the cloning of homologues of smoothened from rat and human. Tissue culture cells expressing the vertebrate Smo protein do not bind N-Shh but the same cells expressing mouse Ptc do bind N-Shh with high affinity. Ptc and Smo can be co-immunoprecipitated from such cells transfected with genes encoding both proteins, indicating that Ptc and Smo physically associate in the membrane.
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Stone D, Hynes M, Armanini M, Swanson T, Gu Q, Johnson R, Scott MP, Pennica D, Goddard A, Phillips H, et al. The tumor-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. of outstanding interest Nature. 384:1996;129-134 Description of the cloning of homologues of smoothened from rat and human. Tissue culture cells expressing the vertebrate Smo protein do not bind N-Shh but the same cells expressing mouse Ptc do bind N-Shh with high affinity. Ptc and Smo can be co-immunoprecipitated from such cells transfected with genes encoding both proteins, indicating that Ptc and Smo physically associate in the membrane.
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Nature
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Stone, D.1
Hynes, M.2
Armanini, M.3
Swanson, T.4
Gu, Q.5
Johnson, R.6
Scott, M.P.7
Pennica, D.8
Goddard, A.9
Phillips, H.10
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16
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The product of hedgehog autoproteolytic cleavage active in local and long-range signaling
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Porter JA, Von Kessler DP, Ekker SC, Young KE, Lee JJ, Moses K, Beachy PA. The product of hedgehog autoproteolytic cleavage active in local and long-range signaling. Nature. 374:1995;363-366.
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Nature
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Porter, J.A.1
Von Kessler, D.P.2
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Lee, J.J.5
Moses, K.6
Beachy, P.A.7
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Cholesterol modification of hedgehog signaling proteins in animal development
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258 during autoproteolytic cleavage of the full-length Hh protein. This results in covalent attachment of the cholesterol moiety to the N-Hh signalling peptide.
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258 during autoproteolytic cleavage of the full-length Hh protein. This results in covalent attachment of the cholesterol moiety to the N-Hh signalling peptide.
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Science
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Porter, J.A.1
Young, K.E.2
Beachy, P.A.3
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0030863352
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Niemann-Pick-c1-disease gene - Homology to mediators of cholesterol homeostasis
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of special interest. Identification of the gene responsible for Niemann-Pick type C disease, which is associated with a defect in cholesterol release. The encoded protein exhibits significant similarity to Patched and with HMG-CoA reductase, the regulatory enzyme of de novo cholesterol biosynthesis.
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Carstea ED, Morris JA, Coleman KG, Loftus SK, Zhang D, Cummings C, Gu J, Rosenfeld MA, Pavan WJ, Krizman DB, et al. Niemann-Pick-c1-disease gene - homology to mediators of cholesterol homeostasis. of special interest Science. 277:1997;228-231 Identification of the gene responsible for Niemann-Pick type C disease, which is associated with a defect in cholesterol release. The encoded protein exhibits significant similarity to Patched and with HMG-CoA reductase, the regulatory enzyme of de novo cholesterol biosynthesis.
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Science
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Carstea, E.D.1
Morris, J.A.2
Coleman, K.G.3
Loftus, S.K.4
Zhang, D.5
Cummings, C.6
Gu, J.7
Rosenfeld, M.A.8
Pavan, W.J.9
Krizman, D.B.10
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19
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Murine model of Niemann-Pick-c-disease - Mutation in a cholesterol homeostasis gene
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of special interest. Cloning and characterisation of the N-PC1 gene from mouse; homology with Patched lies in the putative sterol-sensing domain.
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Loftus SK, Morris JA, Carstea ED, Gu JZ, Cummings C, Brown A, Ellison J, Ohno K, Rosenfeld MA, Tagle DA, et al. Murine model of Niemann-Pick-c-disease - mutation in a cholesterol homeostasis gene. of special interest Science. 277:1997;232-235 Cloning and characterisation of the N-PC1 gene from mouse; homology with Patched lies in the putative sterol-sensing domain.
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Science
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Loftus, S.K.1
Morris, J.A.2
Carstea, E.D.3
Gu, J.Z.4
Cummings, C.5
Brown, A.6
Ellison, J.7
Ohno, K.8
Rosenfeld, M.A.9
Tagle, D.A.10
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20
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Smoothened encodes a serpentine protein required for hedgehog signaling
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of special interest. Germline clonal analysis demonstrates that the segment polarity gene smo is maternally expressed and is absolutely required for Hh signalling in the developing Drosophila embryo. In the imaginal discs, smo acts upstream of PKA to regulate dpp transcription. Cloning and sequence analysis reveals that smo encodes a protein with seven putative membrane-spanning domains.
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Van den Heuvel M, Ingham PW. smoothened encodes a serpentine protein required for hedgehog signaling. of special interest Nature. 382:1996;547-551 Germline clonal analysis demonstrates that the segment polarity gene smo is maternally expressed and is absolutely required for Hh signalling in the developing Drosophila embryo. In the imaginal discs, smo acts upstream of PKA to regulate dpp transcription. Cloning and sequence analysis reveals that smo encodes a protein with seven putative membrane-spanning domains.
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Nature
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Van Den Heuvel, M.1
Ingham, P.W.2
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21
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The Drosophila smoothened gene encodes a 7-pass membrane-protein, a putative receptor for the hedgehog signal
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of special interest. Genetic analysis shows that smo acts downstream of ptc to regulate wg expression in response to hh signalling. Cloning and sequence analysis reveals that smo encodes a protein with seven putative membrane-spanning domains.
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Alcedo J, Ayzenzon M, Vonohlen T, Noll M, Hooper JE. The Drosophila smoothened gene encodes a 7-pass membrane-protein, a putative receptor for the hedgehog signal. of special interest Cell. 86:1996;221-232 Genetic analysis shows that smo acts downstream of ptc to regulate wg expression in response to hh signalling. Cloning and sequence analysis reveals that smo encodes a protein with seven putative membrane-spanning domains.
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(1996)
Cell
, vol.86
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Alcedo, J.1
Ayzenzon, M.2
Vonohlen, T.3
Noll, M.4
Hooper, J.E.5
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Bhanot P, Brink M, Samos CH, Hsieh JC, Wang YS, MacKe JP, Andrew D, Nathans J, Nusse R. A new member of the frizzled family from Drosophila functions as a wingless receptor. Nature. 382:1996;225-230.
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Nature
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Bhanot, P.1
Brink, M.2
Samos, C.H.3
Hsieh, J.C.4
Wang, Y.S.5
MacKe, J.P.6
Andrew, D.7
Nathans, J.8
Nusse, R.9
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Dual roles for patched in sequestering and transducing hedgehog
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of outstanding interest. Clones of cells lacking smo activity are associated with a shift in the domain of dpp activation, consistent with the idea that the failure to express Ptc protein in the absence of smo activity allows Hh protein to diffuse away from its source. This is confirmed by the finding that the dpp domain is similarly distorted by clones of cells homozygous for ptc protein nulls but not by clones expressing mutant forms of Ptc. This is taken to indicate that Ptc interacts directly with Hh, serving to restrict its normal domain of activity.
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Chen Y, Struhl G. Dual roles for patched in sequestering and transducing hedgehog. of outstanding interest Cell. 87:1996;553-563 Clones of cells lacking smo activity are associated with a shift in the domain of dpp activation, consistent with the idea that the failure to express Ptc protein in the absence of smo activity allows Hh protein to diffuse away from its source. This is confirmed by the finding that the dpp domain is similarly distorted by clones of cells homozygous for ptc protein nulls but not by clones expressing mutant forms of Ptc. This is taken to indicate that Ptc interacts directly with Hh, serving to restrict its normal domain of activity.
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Cell
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Chen, Y.1
Struhl, G.2
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Hidalgo, A.1
Ingham, P.2
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Altered neural cell fates and medulloblastoma in mouse patched mutants
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of outstanding interest. Targeted mutation of the murine Ptc gene results in embryonic lethality and, as predicted by analogy to ptc function in Drosophila, transformations of cell fate consistent with a derepression of the Shh pathway. At the level of gene expression, this is manifest in the derepression of transcription of Ptc itself and of Gli1 throughout the ectoderm and mesoderm (but not in the endoderm) as well as of Shh throughout the neural tube.
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Goodrich L, Milenkovic L, Higgins K, Scott M. Altered neural cell fates and medulloblastoma in mouse patched mutants. of outstanding interest Science. 277:1997;1109-1113 Targeted mutation of the murine Ptc gene results in embryonic lethality and, as predicted by analogy to ptc function in Drosophila, transformations of cell fate consistent with a derepression of the Shh pathway. At the level of gene expression, this is manifest in the derepression of transcription of Ptc itself and of Gli1 throughout the ectoderm and mesoderm (but not in the endoderm) as well as of Shh throughout the neural tube.
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Science
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Goodrich, L.1
Milenkovic, L.2
Higgins, K.3
Scott, M.4
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Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity
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Echelard Y, Epstein DJ, St Jacques B, Shen L, Mohler J, McMahon JA, McMahon AP. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell. 75:1993;1417-1430.
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Echelard, Y.1
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St Jacques, B.3
Shen, L.4
Mohler, J.5
McMahon, J.A.6
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Hedgehog and BMP genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo
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Bitgood MJ, McMahon AP. Hedgehog and BMP genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo. Dev Biol. 172:1995;126-138.
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McMahon, A.P.2
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0029750190
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Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein
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of special interest. Elucidation of a paracrine loop whereby Ihh expression in chondrocytes induces PTHRP in perichondrial cells which in turn signals back to the chondrocytes, regulating the progression to hypertrophy.
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Vortkamp A, Lee K, Lanske B, Segre GV, Kronenberg HM, Tabin CJ. Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. of special interest Science. 273:1996;613-622 Elucidation of a paracrine loop whereby Ihh expression in chondrocytes induces PTHRP in perichondrial cells which in turn signals back to the chondrocytes, regulating the progression to hypertrophy.
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Vortkamp, A.1
Lee, K.2
Lanske, B.3
Segre, G.V.4
Kronenberg, H.M.5
Tabin, C.J.6
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Sertoli-cell signaling by desert hedgehog regulates the male germline
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of special interest. Murine Dhh is normally expressed in Sertoli cells whilst high levels of Ptc expression are seen in associated Leydig cells. Targeted mutation of the Dhh gene leads to the loss of Ptc expression and the complete absence of mature sperm, suggesting that Dhh regulates germline differentiation by signalling to the androgen-producing Leydig cells.
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Bitgood MJ, Shen LY, McMahon AP. Sertoli-cell signaling by desert hedgehog regulates the male germline. of special interest Curr Biol. 6:1996;298-304 Murine Dhh is normally expressed in Sertoli cells whilst high levels of Ptc expression are seen in associated Leydig cells. Targeted mutation of the Dhh gene leads to the loss of Ptc expression and the complete absence of mature sperm, suggesting that Dhh regulates germline differentiation by signalling to the androgen-producing Leydig cells.
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Bitgood, M.J.1
Shen, L.Y.2
McMahon, A.P.3
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Takabatake T, Ogawa M, Takahashi TC, Mizuno M, Okamoto M, Takeshima K. Hedgehog and patched gene-expression in adult ocular-tissues. FEBS Lett. 410:1997;485-489.
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Takeshima, K.6
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Most germ-line mutations in the nevoid basal-cell carcinoma syndrome lead to a premature termination of the patched protein, and no genotype-phenotype correlations are evident
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Wicking C, Shanley S, Smyth I, Gillies S, Negus K, Graham S, Suthers G, Haites N, Edwards M, Wainwright B, Chenevixtrench G. Most germ-line mutations in the nevoid basal-cell carcinoma syndrome lead to a premature termination of the patched protein, and no genotype-phenotype correlations are evident. Am J Hum Genet. 60:1997;21-26.
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Mutations in the human homolog of the Drosophila patched gene in Caucasian and African-American nevoid basal-cell carcinoma syndrome patients
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Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly
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Mutations in the human homolog of Drosophila patched (ptch) in basal-cell carcinomas and the gorlin syndrome - Different in vivo mechanisms of ptch inactivation
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Unden AB, Holmberg E, Lundhrozell B, Stahlebackdahl M, Zaphiropoulos PG, Toftgard R, Vorechovsky I. Mutations in the human homolog of Drosophila patched (ptch) in basal-cell carcinomas and the gorlin syndrome - different in vivo mechanisms of ptch inactivation. Cancer Res. 56:1996;4562-4565.
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Induction of basal-cell carcinoma features in transgenic human skin expressing sonic hedgehog
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of outstanding interest. Overexpression of SHH in human keratinocytes causes elevated expression of BMP-2B and of bcl-2, the latter effect being typical of BCCs. These cells also regenerate skin displaying histological features typical of BCCs when grafted onto nude mice, suggesting that activation of the Shh pathway is sufficient for the formation of basal cell tumours.
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Fan HR, Oro AE, Scott MP, Khavari PA. Induction of basal-cell carcinoma features in transgenic human skin expressing sonic hedgehog. of outstanding interest Nat Med. 3:1997;788-792 Overexpression of SHH in human keratinocytes causes elevated expression of BMP-2B and of bcl-2, the latter effect being typical of BCCs. These cells also regenerate skin displaying histological features typical of BCCs when grafted onto nude mice, suggesting that activation of the Shh pathway is sufficient for the formation of basal cell tumours.
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Basal-cell carcinomas in mice overexpressing Sonic hedgehog
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of special interest. Transgenic mice in which expression of the Shh-coding region is driven by the keratin 14 promoter develop skin abnormalities similar to those seen in BCCs, a finding consistent with the notion that inappropriate activation of the Hh signalling pathway is sufficient to induce tumour formation.
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Oro AE, Higgins KM, Hu ZL, Bonifas JM, Epstein EH, Scott MP. Basal-cell carcinomas in mice overexpressing Sonic hedgehog. of special interest Science. 276:1997;817-821 Transgenic mice in which expression of the Shh-coding region is driven by the keratin 14 promoter develop skin abnormalities similar to those seen in BCCs, a finding consistent with the notion that inappropriate activation of the Hh signalling pathway is sufficient to induce tumour formation.
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Hedgehog is required for the proliferation and specification of ovarian somatic-cells prior to egg chamber formation in Drosophila
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of special interest. Analysis of hh expression during oogenesis shows that it is specifically expressed in a specialised group of cells - the terminal filament - at the tip of each ovariole. This expression is required for the proliferation of the somatic pre-follicle cells and specifies follicle cell identity. Misexpression of hh leads to hyperplasia of these cells.
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Forbes AJ, Lin HF, Ingham PW, Spradling AC. Hedgehog is required for the proliferation and specification of ovarian somatic-cells prior to egg chamber formation in Drosophila. of special interest Development. 122:1996;1125-1135 Analysis of hh expression during oogenesis shows that it is specifically expressed in a specialised group of cells - the terminal filament - at the tip of each ovariole. This expression is required for the proliferation of the somatic pre-follicle cells and specifies follicle cell identity. Misexpression of hh leads to hyperplasia of these cells.
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The role of segment polarity genes during early oogenesis in Drosophila
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of special interest. ptc is expressed at high levels in the ovary within 10 cell diameters of hh-expressing cells. Removal of Ptc function leads to overproliferation of the pre-follicle cells, implying that Hh activity normally controls the proliferation of these cells.
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Forbes AJ, Spradling AC, Ingham PW, Lin HF. The role of segment polarity genes during early oogenesis in Drosophila. of special interest Development. 122:1996;3283-3294 ptc is expressed at high levels in the ovary within 10 cell diameters of hh-expressing cells. Removal of Ptc function leads to overproliferation of the pre-follicle cells, implying that Hh activity normally controls the proliferation of these cells.
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The role of the human homolog of Drosophila patched in sporadic basal-cell carcinomas
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of special interest. SSCP analysis of 37 sporadic BCCs reveals that one third carry mutations in PTCH. Direct sequencing of two SSCP negative samples revealed mutations in these tumours too, indicating that SSCP analysis underestimates the frequency of mutation. Expression analysis shows that PTCH is expressed at high levels in tumour cells but not in normal skin.
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Gailani MR, Stahlebackdahl M, Leffell DJ, Glynn M, Zaphiropoulos PG, Pressman C, Unden AB, Dean M, Brash DE, Bale AE, Toftgard R. The role of the human homolog of Drosophila patched in sporadic basal-cell carcinomas. of special interest Nat Genet. 14:1996;78-81 SSCP analysis of 37 sporadic BCCs reveals that one third carry mutations in PTCH. Direct sequencing of two SSCP negative samples revealed mutations in these tumours too, indicating that SSCP analysis underestimates the frequency of mutation. Expression analysis shows that PTCH is expressed at high levels in tumour cells but not in normal skin.
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Mutations in the human homolog of the Drosophila segment polarity gene patched (ptch) in sporadic basal-cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system
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Wolter M, Reifenberger J, Sommer C, Ruzicka T, Reifenberger G. Mutations in the human homolog of the Drosophila segment polarity gene patched (ptch) in sporadic basal-cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res. 57:1997;2581-2585.
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Medulloblastomas of the desmoplastic variant carry mutations of the human homolog of Drosophila patched
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Pietsch T, Waha A, Koch A, Kraus J, Albrecht S, Tonn J, Sorensen N, Berthold F, Henk B, Schmandt N, et al. Medulloblastomas of the desmoplastic variant carry mutations of the human homolog of Drosophila patched. Cancer Res. 57:(N11):1997;2085-2088.
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Pietsch, T.1
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43
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Mutations of the patched gene in several types of sporadic extracutaneous tumors
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Xie JW, Johnson RL, Zhang XL, Bare JW, Waldman FM, Cogen PH, Menon AG, Warren RS, Chen LC, Scott MP, Epstein EH. Mutations of the patched gene in several types of sporadic extracutaneous tumors. Cancer Res. 57:1997;2369-2372.
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44
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Somatic mutations in the human homolog of Drosophila patched in primitive neuroectodermal tumors
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Vorechovsky I, Tingby O, Hartman M, Stromberg B, Nister M, Collins VP, Toftgard R. Somatic mutations in the human homolog of Drosophila patched in primitive neuroectodermal tumors. Oncogene. 15:1997;361-366.
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45
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Human patched (PTCH) messenger-RNA is overexpressed consistently in tumor-cells of both familial and sporadic basal-cell carcinoma
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of special interest. In situ hybridisation analysis shows that PTCH transcription is deregulated in all BCCs irrespective of their histological phenotype or the presence of a PTCH mutation, implying that loss of PTCH regulation is an early rate-limiting step in BCC development.
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Unden AB, Zaphiropoulos PG, Bruce K, Toftgard R, Stahlebackdahl M. Human patched (PTCH) messenger-RNA is overexpressed consistently in tumor-cells of both familial and sporadic basal-cell carcinoma. of special interest Cancer Res. 57:1997;2336-2340 In situ hybridisation analysis shows that PTCH transcription is deregulated in all BCCs irrespective of their histological phenotype or the presence of a PTCH mutation, implying that loss of PTCH regulation is an early rate-limiting step in BCC development.
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Cancer Res
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Unden, A.B.1
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46
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0031587830
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Proteolysis that is inhibited by hedgehog targets cubitus-interruptus protein to the nucleus and converts it to a repressor
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of outstanding interest. The authors demonstrate that the Cubitus interruptus protein - previously implicated in Hh signal transduction - is subject to proteolytic cleavage. The cleaved form of the protein is shown to have transcriptional repressing activity in contrast to the activating activity of the full-length protein. Cleavage is shown to be inhibited by Hh activity, thus suggesting a mechanism by which Hh signalling can regulate transcription.
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Aza-Blanc P, Ramirezweber F, Laget M, Schwartz C, Kornberg T. Proteolysis that is inhibited by hedgehog targets cubitus-interruptus protein to the nucleus and converts it to a repressor. of outstanding interest Cell. 89:1997;1043-1053 The authors demonstrate that the Cubitus interruptus protein - previously implicated in Hh signal transduction - is subject to proteolytic cleavage. The cleaved form of the protein is shown to have transcriptional repressing activity in contrast to the activating activity of the full-length protein. Cleavage is shown to be inhibited by Hh activity, thus suggesting a mechanism by which Hh signalling can regulate transcription.
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Cell
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Aza-Blanc, P.1
Ramirezweber, F.2
Laget, M.3
Schwartz, C.4
Kornberg, T.5
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47
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0030844141
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Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours
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of outstanding interest. Ectopic expression of Gli1 in Xenopus embryos causes tumours of the epidermis. Gli1 is not normally expressed in human interfollicular basal cells but is ectopically expressed in nearly all BCCs analysed.
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Dahmane N, Lee J, Robins P, Heller P, Ruiz i Altaba A. Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours. of outstanding interest Nature. 389:1997;876-881 Ectopic expression of Gli1 in Xenopus embryos causes tumours of the epidermis. Gli1 is not normally expressed in human interfollicular basal cells but is ectopically expressed in nearly all BCCs analysed.
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Nature
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Dahmane, N.1
Lee, J.2
Robins, P.3
Heller, P.4
Ruiz I Altaba, A.5
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48
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0030754171
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Costal2, a novel kinesin-related protein in the Hedgehog signaling pathway
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of outstanding interest. Molecular characterisation of the costal-2 gene that acts downstream of ptc to repress the Hh signalling pathway in Drosophila indicates that it encodes a kinesin-related protein that binds to microtubules and interacts with the Cubitus interruptus protein (a Drosophila Gli homologue).
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Sisson J, Ho K, Suyama K, Scott MP. Costal2, a novel kinesin-related protein in the Hedgehog signaling pathway. of outstanding interest Cell. 90:1997;235-245 Molecular characterisation of the costal-2 gene that acts downstream of ptc to repress the Hh signalling pathway in Drosophila indicates that it encodes a kinesin-related protein that binds to microtubules and interacts with the Cubitus interruptus protein (a Drosophila Gli homologue).
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Cell
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Sisson, J.1
Ho, K.2
Suyama, K.3
Scott, M.P.4
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49
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0030838880
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Hedgehog elicits signal transduction by means of a large complex containing the kinesin-related protein Costal2
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of outstanding interest. Identification of Costal-2 as a component of a multiprotein complex that binds to microtubules and includes the Fused and Cubitus interruptus proteins. Microtubule binding is regulated by Hh signalling, and the Hh-induced dissociation apparently facilitates activation of the Cubitus interruptus.
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Robbins DJ, Nybakken KE, Kobayashi R, Sisson JC, Bishop JM, Preat TP. Hedgehog elicits signal transduction by means of a large complex containing the kinesin-related protein Costal2. of outstanding interest Cell. 90:1997;225-234 Identification of Costal-2 as a component of a multiprotein complex that binds to microtubules and includes the Fused and Cubitus interruptus proteins. Microtubule binding is regulated by Hh signalling, and the Hh-induced dissociation apparently facilitates activation of the Cubitus interruptus.
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Cell
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Robbins, D.J.1
Nybakken, K.E.2
Kobayashi, R.3
Sisson, J.C.4
Bishop, J.M.5
Preat, T.P.6
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