Skip to main content
SpringerLink
Log in

Hedgehog Signaling in Animal Development and Human Disease

  • Conference paper
Of Fish, Fly, Worm, and Man

Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 29))

Abstract

Higher eukaryotes have developed a number of mechanisms to address the challenge of progressing from a single-cell zygote to a multicellular adult organism. Forming complex structures such as a wing, eye, or a spinal cord requires precise control of cell growth and differentiation. Generating spatial patterns in embryogenesis requires communication between adjacent cells, and secreted proteins are one way by which neighboring cells relay information. The Hedgehog (Hh) family of secreted proteins is critical for the embryonic development of many animals. Hh signaling mechanisms thus provide a window into early development and pattern formation. Genetic screens using Drosophila have revealed a number of components involved in Hh signaling. For many of them, their vertebrate counterparts have been found and this pathway is conserved to a remarkable degree. Furthermore, several components involved in Hh signaling are mutated in human tumors and developmental syndromes, highlighting the importance of this pathway in disease. Recent work has focused on understanding how the various components of the Hh pathway receive and transduce the Hh signal to control cell fate and proliferation decisions. The dissection of the Hh pathway has provided valuable insights into the basic mechanisms of development and disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ahn J, Ludecke HJ, Lindow S, Horton WA, Lee B, Wagner MJ, Horsthemke B, Wells DE (1995) Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1). Nat Genet 11: 137–143

    Article  PubMed  CAS  Google Scholar 

  • Akimaru H, Chen Y, Dai P, Hou DX, Nonaka M, Smolik SM, Armstrong S, Goodman RH, Ishii S (1997) Drosophila CBP is a co-activator of cubitus interruptus in hedgehog signalling. Nature 386: 735–738

    Google Scholar 

  • Alcedo J, Ayzenzon M, Von Ohlen T, Noll M, Hooper JE (1996) The Drosophila smoothened gene encodes a seven-pass membrane protein, a putative receptor for the hedgehog signal. Cell 86: 221–232

    Article  PubMed  CAS  Google Scholar 

  • Alves G, Limbourg-Bouchon B, Tricoire H, Brissard-Zahraoui J, Lamour-Isnard C, Busson D (1998) Modulation of hedgehog target gene expression by the fused serine-threonine kinase in wing imaginal discs. Mech Dev 78: 17–31

    Article  PubMed  CAS  Google Scholar 

  • Aszterbaum M, Rothman A, Johnson RL, Fisher M, Xie J, Bonifas JM, Zhang X, Scott MP, Epstein EH Jr (1998) Identification of mutations in the human PATCHED gene in sporadic basal cell carcinomas and in patients with the basal cell nevus syndrome. J Invest Dermatol 110: 885–888

    Article  PubMed  CAS  Google Scholar 

  • Aza-Blanc P, Ramirez-Weber FA, Laget MP, Schwartz C, Kornberg TB (1997) Proteolysis that is inhibited by hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a repressor. Cell 89: 1043–1053

    Article  PubMed  CAS  Google Scholar 

  • Bellaiche Y, The I, Perrimon N (1998) Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion. Nature 394: 85–88

    CAS  Google Scholar 

  • Belloni E, Muenke M, Roessler E, Traverso G, Siegel-Bartelt J, Frumkin A, Mitchell HF, Donis-Keller H, Helms C, Hing AV, Heng HH, Koop B, Martindale D, Rommens JM, Tsui LC, Scherer SW (1996) Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly. Nat Genet 14: 353–356

    Article  PubMed  CAS  Google Scholar 

  • Bitgood MJ, Shen L, McMahon AP (1996) Sertoli cell signaling by Desert hedgehog regulates the male germline. Curr Biol 6: 298–304

    Article  PubMed  CAS  Google Scholar 

  • Bumcrot DA, Takada R, McMahon AP (1995) Proteolytic processing yields two secreted forms of sonic hedgehog. Mol Cell Biol 15: 2294–2303

    PubMed  CAS  Google Scholar 

  • Capdevila J, Pariente F, Sampedro J, Alonso JL, Guerrero I (1994) Subcellular localization of the segment polarity protein patched suggests an interaction with the wingless reception complex in Drosophila embryos. Development 120: 987–998

    PubMed  CAS  Google Scholar 

  • Carpenter D, Stone DM, Brush J, Ryan A, Armanini M, Frantz G, Rosenthal A, de Sauvage FJ (1998) Characterization of two patched receptors for the vertebrate hedgehog protein family. Proc Natl Acad Sci USA 95: 13630–13634

    Article  PubMed  CAS  Google Scholar 

  • Carstea ED, Morris JA, Coleman KG, Loftus SK, Zhang D, Cummings C, Gu J, Rosenfeld MA, Pavan WJ, Krizman DB, Nagle J, Polymeropoulos MH, Sturley SL, Ioannou YA, Higgins ME, Comly M, Cooney A, Brown A, Kaneski CR, Blanchette-Mackie EJ, Dwyer NK, Neufeld EB, Chang TY, Liscum L, Strauss JF, Ohno K, Zeigler M, Carmi R, Sokol J, Markie D, O’Neill RR, van Diggelen OP, Elleder M, Patterson MC, Brady RO, Vanier MT, Pentchev PG, Tagle DA (1997) Niemann-Pick Cl disease gene: homology to mediators of cholesterol homeostasis. Science 277: 228–231

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Struhl G (1996) Dual roles for patched in sequestering and transducing Hedgehog. Cell 87: 553–563

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Struhl G (1998) In vivo evidence that Patched and Smoothened constitute distinct binding and transducing components of a Hedgehog receptor complex. Development 125: 4943–4948

    PubMed  CAS  Google Scholar 

  • Chiang C, Litingtung Y, Lee E, Young KE, Corden JL, Westphal H, Beachy PA (1996) Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383: 407–413

    Article  PubMed  CAS  Google Scholar 

  • Chidambaram A, Goldstein AM, Gailani MR, Gerrard B, Bale SJ, DiGiovanna JJ, Bale AE, Dean M (1996) Mutations in the human homologue of the Drosophila patched gene in Caucasian and African-American nevoid basal cell carcinoma syndrome patients. Cancer Res 56: 4599–4601

    PubMed  CAS  Google Scholar 

  • Concordet JP, Lewis KE, Moore JW, Goodrich LV, Johnson RL, Scott MP, Ingham PW (1996) Spatial regulation of a zebrafish patched homologue reflects the roles of sonic hedgehog and protein kinase A in neural tube and somite patterning. Development 122: 2835–2846

    PubMed  CAS  Google Scholar 

  • Cooper MK, Porter JA, Young KE, Beachy PA (1998) Teratogen-mediated inhibition of target tissue response to Shh signaling. Science 280:1603–1607 de Kretser DM, Loveland KL, Meinhardt A, Simorangkir D, Wreford N (1998) Spermatogenesis. Hum Reprod 13: 1–8

    Google Scholar 

  • Epps JL, Jones JB, Tanda S (1997) oroshigane, a new segment polarity gene of Drosophila melanogaster, functions in hedgehog signal transduction. Genetics 145: 1041–1052

    Google Scholar 

  • Evans DG, Farndon PA, Burnell LD, Gattamaneni HR, Birch JM (1991) The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma. Br J Cancer 64: 959–961

    Article  PubMed  CAS  Google Scholar 

  • Fan H, Oro AE, Scott MP, Khavari PA (1997) Induction of basal cell carcinoma features in transgenic human skin expressing Sonic Hedgehog. Nat Med 3: 788–792

    Article  PubMed  CAS  Google Scholar 

  • Fitzky BU, Witsch-Baumgartner M, Erdel M, Lee JN, Paik YK, Glossmann H, Utermann G, Moebius FF (1998) Mutations in the Delta7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome. Proc Natl Acad Sci USA 95: 8181–8186

    Article  PubMed  CAS  Google Scholar 

  • Gailani MR, Stahle-Backdahl M, Leffell DJ, Glynn M, Zaphiropoulos PG, Pressman C, Unden AB, Dean M, Brash DE, Bale AE, Toftgard R (1996) The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat Genet 14: 78–81

    Article  PubMed  CAS  Google Scholar 

  • Gayther SA, Warren W, Mazoyer S, Russell PA, Harrington PA, Chiano M, Seal S, Hamoudi R, van Rensburg EJ, Dunning AM, et al. (1995) Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation. Nat Genet 11: 428–433

    Article  PubMed  CAS  Google Scholar 

  • Goodrich LV, Johnson RL, Milenkovic L, McMahon JA, Scott MP (1996) Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog. Genes Dev 10: 301–312

    Article  PubMed  CAS  Google Scholar 

  • Goodrich LV, Milenkovic L, Higgins KM, Scott MP (1997) Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277: 1109–1113

    Article  PubMed  CAS  Google Scholar 

  • Gorlin RJ (1995) Nevoid basal cell carcinoma syndrome. Dermatol Clin 13: 113–125

    PubMed  CAS  Google Scholar 

  • Grindley JC, Bellusci S, Perkins D, Hogan BL (1997) Evidence for the involvement of the Gli gene family in embryonic mouse lung development. Dev Biol 188: 337–348

    Article  PubMed  CAS  Google Scholar 

  • Griswold MD (1995) Interactions between germ cells and Sertoli cells in the testis. Biol Reprod 52: 211–216

    Article  PubMed  CAS  Google Scholar 

  • Hahn H, Wicking C, Zaphiropoulous PG, Gailani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B, Bale AE (1996) Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85: 841–851

    Article  PubMed  CAS  Google Scholar 

  • Hahn H, Wojnowski L, Zimmer AM, Hall J, Miller G, Zimmer A (1998) Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome. Nat Med 4: 619–622

    Article  PubMed  CAS  Google Scholar 

  • Hidalgo A (1991) Interactions between segment polarity genes and the generation of the segmental pattern in Drosophila. Mech Dev 35: 77–87

    Article  PubMed  CAS  Google Scholar 

  • Hidalgo A, Ingham P (1990) Cell patterning in the Drosophila segment: spatial regulation of the segment polarity gene patched. Development 110: 291–301

    PubMed  CAS  Google Scholar 

  • Hooper JE, Scott MP (1989) The Drosophila patched gene encodes a putative membrane protein required for segmental patterning. Cell 59: 751–765

    Article  PubMed  CAS  Google Scholar 

  • Hui CC, Joyner AL (1993) A mouse model of Greig cephalopolysyndactyly syndrome: the extra-toes mutation contains an intragenic deletion of the Gli3 gene. Nat Genet 3: 241–246

    Article  PubMed  CAS  Google Scholar 

  • Hynes M, Stone DM, Dowd M, Pitts-Meek S, Goddard A, Gurney A, Rosenthal A (1997) Control of cell pattern in the neural tube by the zinc finger transcription factor and oncogene Gli-1. Neuron 19: 15–26

    Article  PubMed  CAS  Google Scholar 

  • Incardona JP, Gaffield W, Kapur RP, Roelink H (1998) The teratogenic Veratrum alkaloid cyclopamine inhibits sonic hedgehog signal transduction. Development 125: 3553–3562

    PubMed  CAS  Google Scholar 

  • Ingham PW, Taylor AM, Nakano Y (1991) Role of the Drosophila patched gene in positional signalling. Nature 353: 184–187

    Article  PubMed  CAS  Google Scholar 

  • Jiang J, Struhl G (1995) Protein kinase A and hedgehog signaling in Drosophila limb development. Cell 80: 563–572

    Article  PubMed  CAS  Google Scholar 

  • Jiang J, Struhl G (1998) Regulation of the Hedgehog and Wingless signalling pathways by the F- box/WD40-repeat protein Slimb. Nature 391: 493–496

    Article  PubMed  CAS  Google Scholar 

  • Jingami H, Brown MS, Goldstein JL, Anderson RG, Luskey KL (1987) Partial deletion of membrane-bound domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase eliminates sterol-enhanced degradation and prevents formation of crystalloid endoplasmic reticulum. J Cell Biol 104: 1693–1704

    Article  PubMed  CAS  Google Scholar 

  • Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein E Jr, Scott MP (1996) Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 272: 1668–1671

    Article  PubMed  CAS  Google Scholar 

  • Kang S, Graham J, Jr., Olney AH, Biesecker LG (1997) GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome. Nat Genet 15: 266–268

    Article  PubMed  CAS  Google Scholar 

  • Keeler RF (1975) Teratogenic effects of cyclopamine and jervine in rats, mice and hamsters. Proc Soc Exp Biol Med 149: 302–306

    PubMed  CAS  Google Scholar 

  • Keeler RF (1978) Cyclopamine and related steroidal alkaloid teratogens: their occurrence, structural relationship, and biologic effects. Lipids 13: 708–715

    Article  PubMed  CAS  Google Scholar 

  • Kim SK, Melton DA (1998) Pancreas development is promoted by cyclopamine, a hedgehog signaling inhibitor. Proc Natl Acad Sci USA 95: 13036–13041

    Article  PubMed  CAS  Google Scholar 

  • Kinzler KW, Bigner SH, Bigner DD, Trent JM, Law ML, O’Brien SJ, Wong AJ, Vogelstein B (1987) Identification of an amplified, highly expressed gene in a human glioma. Science 236: 70–73

    Article  PubMed  CAS  Google Scholar 

  • Kinzler KW, Ruppert JM, Bigner SH, Vogelstein B (1988) The GLI gene is a member of the Kruppel family of zinc finger proteins. Nature 332: 371–374

    Article  PubMed  CAS  Google Scholar 

  • Kumagai H, Chun KT, Simoni RD (1995) Molecular dissection of the role of the membrane domain in the regulated degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase. J Biol Chem 270: 19107–19113

    Article  PubMed  CAS  Google Scholar 

  • Lee JJ, von Kessler DP, Parks S, Beachy PA (1992) Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog. Cell 71: 33–50

    Article  PubMed  CAS  Google Scholar 

  • Lee JJ, Ekker SC, von Kessler DP, Porter JA, Sun BI, Beachy PA (1994) Auto-proteolysis in hedgehog protein biogenesis. Science 266: 1528–1537

    Article  PubMed  CAS  Google Scholar 

  • Lepage T, Cohen SM, Diaz-Benjumea FJ, Parkhurst SM (1995) Signal transduction by cAMP-dependent protein kinase A in Drosophila limb patterning. Nature 373: 711–715

    Article  PubMed  CAS  Google Scholar 

  • Li W, Ohlmeyer JT, Lane ME, Kalderon D (1995) Function of protein kinase A in hedgehog signal transduction and Drosophila imaginal disc development. Cell 80: 553–562

    Article  PubMed  CAS  Google Scholar 

  • Liscum L, Faust JR (1987) Low density lipoprotein ( LDL)-mediated suppression of cholesterol synthesis and LDL uptake is defective in Niemann-Pick type C fibroblasts. J Biol Chem 262: 17002–17008

    Google Scholar 

  • Litingtung Y, Lei L, Westphal H, Chiang C (1998) Sonic hedgehog is essential to foregut development. Nat Genet 20: 58–61

    Article  PubMed  CAS  Google Scholar 

  • Loftus SK, Morris JA, Carstea ED, Gu JZ, Cummings C, Brown A, Ellison J, Ohno K, Rosenfeld MA, Tagle DA, Pentchev PG, Pavan WJ (1997) Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene. Science 277: 232–235

    Article  PubMed  CAS  Google Scholar 

  • Maesawa C, Tamura G, Iwaya T, Ogasawara S, Ishida K, Sato N, Nishizuka S, Suzuki Y, Ikeda K, Aoki K, Saito K, Satodate R (1998) Mutations in the human homologue of the Drosophila patched gene in esophageal squamous cell carcinoma. Genes Chromosomes Cancer 21: 276–279

    Article  PubMed  CAS  Google Scholar 

  • Marigo V, Tabin CJ (1996) Regulation of patched by Sonic hedgehog in the developing neural tube. Proc Natl Acad Sci USA 93: 9346–9351

    Article  PubMed  CAS  Google Scholar 

  • Marigo V, Davey RA, Zuo Y, Cunningham JM, Tabin CJ (1996) Biochemical evidence that patched is the Hedgehog receptor. Nature 384: 176–179

    Article  PubMed  CAS  Google Scholar 

  • Marigo V, Johnson RL, Vortkamp A, Tabin CJ (1996) Sonic hedgehog differentially regulates expression of GLI and GLI3 during limb development. Dev Biol 180: 273–283

    Article  PubMed  CAS  Google Scholar 

  • McGarvey TW, Maruta Y, Tomaszewski JE, Linnenbach A.1, Malkowicz SB (1998) PTCH gene mutations in invasive transitional cell carcinoma of the bladder. Oncogene 17: 1167–1172

    CAS  Google Scholar 

  • Miller DL, Weinstock MA (1994) Nonmelanoma skin cancer in the United States: incidence. J Am Acad Dermatol 30: 774–778

    Article  PubMed  CAS  Google Scholar 

  • Mohler J, Vani K (1992) Molecular organization and embryonic expression of the hedgehog gene involved in cell—cell communication in segmental patterning of Drosophila. Development 115: 957–971

    PubMed  CAS  Google Scholar 

  • Monnier V, Dussillol F, Alves G, Lamour-Isnard C, Plessis A (1998) Suppressor of fused links fused and Cubitus interruptus on the hedgehog signalling pathway. Curr Biol 8: 583–586

    Article  PubMed  CAS  Google Scholar 

  • Motoyama J, Heng H, Crackower MA, Takabatake T, Takeshima K, Tsui LC, Hui C (1998) Overlapping and non-overlapping ptch2 expression with shh during mouse embryogenesis. Mech Dev 78: 81–84

    Article  PubMed  CAS  Google Scholar 

  • Motoyama J, Liu J, Mo R, Ding Q, Post M, Hui CC (1998) Essential function of Gli2 and Gli3 in the formation of lung, trachea and oesophagus. Nat Genet 20: 54–57

    Article  PubMed  CAS  Google Scholar 

  • Motoyama J, Takabatake T, Takeshima K, Hui C (1998) Ptch2, a second mouse Patched gene is co-expressed with Sonic hedgehog. Nat Genet 18: 104–106

    Article  PubMed  CAS  Google Scholar 

  • Motzny CK, Holmgren R (1995) The Drosophila Cubitus interruptus protein and its role in the wingless and hedgehog signal transduction pathways. Mech Dev 52: 137–150

    Article  PubMed  CAS  Google Scholar 

  • Nakano Y, Guerrero I, Hidalgo A, Taylor A, Whittle JR, Ingham PW (1989) A protein with several possible membrane-spanning domains encoded by the Drosophila segment polarity gene patched. Nature 341: 508–513

    Article  PubMed  CAS  Google Scholar 

  • Nohturfft A, Hua X, Brown MS, Goldstein JL (1996) Recurrent G-to-A substitution in a single codon of SREBP cleavage-activating protein causes sterol resistance in three mutant Chinese hamster ovary cell lines. Proc Natl Acad Sci USA 93: 13709–13714

    Article  PubMed  CAS  Google Scholar 

  • Nohturfft A, Brown MS, Goldstein JL (1998) Topology of SREBP cleavage-activating protein, a polytopic membrane protein with a sterol-sensing domain. J Biol Chem 273: 17243–17250

    Article  PubMed  CAS  Google Scholar 

  • Nusslein-Volhard C, Wieschaus E (1980) Mutations affecting segment number and polarity in Drosophila. Nature 287: 795–801

    Article  PubMed  CAS  Google Scholar 

  • Ohlmeyer JT, Kalderon D (1998) Hedgehog stimulates maturation of Cubitus interruptus into a labile transcriptional activator. Nature 396: 749–753

    Article  PubMed  CAS  Google Scholar 

  • Orenic TV, Slusarski DC, Kroll KL, Holmgren RA (1990) Cloning and characterization of the segment polarity gene Cubitus interruptus Dominant of Drosophila. Genes Dev 4: 1053–1067

    Article  PubMed  CAS  Google Scholar 

  • Oro AE, Higgins KM, Hu Z, Bonifas JM, Epstein E, Jr., Scott MP (1997) Basal cell carcinomas in mice overexpressing sonic hedgehog. Science 276: 817–821

    Article  PubMed  CAS  Google Scholar 

  • Pan D, Rubin GM (1995) cAMP-dependent protein kinase and hedgehog act antagonistically in regulating decapentaplegic transcription in Drosophila imaginal discs. Cell 80: 543–552

    Google Scholar 

  • Pentchev PG, Comly ME, Kruth HS, Tokoro T, Butler J, Sokol J, Filling-Katz M, Quirk JM, Marshall DC, Patel S (1987) Group C Niemann-Pick disease: faulty regulation of low-density lipoprotein uptake and cholesterol storage in cultured fibroblasts. FASEB J 1: 40–45

    PubMed  CAS  Google Scholar 

  • Pham A, Therond P, Alves G, Tournier FB, Busson D, Lamour-Isnard C, Bouchon BL, Preat T, Tricoire H (1995) The Suppressor of fused gene encodes a novel PEST protein involved in Drosophila segment polarity establishment. Genetics 140: 587–598

    PubMed  CAS  Google Scholar 

  • Pietsch T, Waha A, Koch A, Kraus J, Albrecht S, Tonn J, Sorensen N, Berthold F, Henk B, Schmandt N, Wolf HK, von Deimling A, Wainwright B, Chenevix-Trench G, Wiestler OD, Wicking C (1997) Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched. Cancer Res 57: 2085–2088

    PubMed  CAS  Google Scholar 

  • Porter JA, von Kessler DP, Ekker SC, Young KE, Lee JJ, Moses K, Beachy PA (1995) The product of hedgehog autoproteolytic cleavage active in local and long-range signalling. Nature 374: 363–366

    Article  PubMed  CAS  Google Scholar 

  • Porter JA, Young KE, Beachy PA (1996) Cholesterol modification of hedgehog signaling proteins in animal development. Science 274: 255–259

    Article  PubMed  CAS  Google Scholar 

  • Preat T, Therond P, Lamour-Isnard C, Limbourg-Bouchon B, Tricoire H, Erk I, Mariol MC, Busson D (1990) A putative serine/threonine protein kinase encoded by the segment-polarity fused gene of Drosophila. Nature 347: 87–89

    Article  PubMed  CAS  Google Scholar 

  • Radhakrishna U, Wild A, Grzeschik KH, Antonarakis SE (1997) Mutation in GLI3 in postaxial polydactyly type A. Nat Genet 17: 269–271

    Article  PubMed  CAS  Google Scholar 

  • Raffel C, Jenkins RB, Frederick L, Hebrink D, Alderete B, Fults DW, James CD (1997) Sporadic medulloblastomas contain PTCH mutations. Cancer Res 57: 842–845

    PubMed  CAS  Google Scholar 

  • Reifenberger J, Wolter M, Weber RG, Megahed M, Ruzicka T, Lichter P, Reifenberger G (1998) Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res 58: 1798–1803

    PubMed  CAS  Google Scholar 

  • Robbins DJ, Nybakken KE, Kobayashi R, Sisson JC, Bishop JM, Therond PP (1997) Hedgehog elicits signal transduction by means of a large complex containing the kinesin-related protein costal2. Cell 90: 225–234

    Article  PubMed  CAS  Google Scholar 

  • Roelink H, Augsburger A, Heemskerk J, Korzh V, Norlin S, Ruiz i Altaba A, Tanabe Y, Placzek M, Edlund T, Jessell TM (1994) Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord. Cell 76: 761–775

    Article  PubMed  CAS  Google Scholar 

  • Roelink H, Porter JA, Chiang C, Tanabe Y, Chang DT, Beachy PA, Jessell TM (1995) Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis. Cell 81: 445–455

    Article  PubMed  CAS  Google Scholar 

  • Roessler E, Belloni E, Gaudenz K, Jay P, Berta P, Scherer SW, Tsui LC, Muenke M (1996) Mutations in the human Sonic Hedgehog gene cause holoprosencephaly. Nat Genet 14: 357–360

    Article  PubMed  CAS  Google Scholar 

  • Roessler E, Belloni E, Gaudenz K, Vargas F, Scherer SW, Tsui LC, Muenke M (1997) Mutations in the C-terminal domain of Sonic Hedgehog cause holoprosencephaly. Hum Mol Genet 6: 1847–1853

    Article  PubMed  CAS  Google Scholar 

  • Ruppert JM, Kinzler KW, Wong AJ, Bigner SH, Kao FT, Law ML, Seuanez HN, O’Brien SJ, Vogelstein B (1988) The GLI-Kruppel family of human genes. Mol Cell Biol 8: 3104–3113

    PubMed  CAS  Google Scholar 

  • Ruppert JM, Vogelstein B, Arheden K, Kinzler KW (1990) GLI3 encodes a 190-kilodalton protein with multiple regions of GLI similarity. Mol Cell Biol 10: 5408–5415

    PubMed  CAS  Google Scholar 

  • Sisson JC, Ho KS, Suyama K, Scott MP (1997) Costal2, a novel kinesin-related protein in the Hedgehog signaling pathway. Cell 90: 235–245

    Article  PubMed  CAS  Google Scholar 

  • Stone DM, Hynes M, Armanini M, Swanson TA, Gu Q, Johnson RL, Scott MP, Pennica D, Goddard A, Phillips H, Noll M, Hooper JE, de Sauvage F, Rosenthal A (1996) The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature 384: 129–134

    Article  PubMed  CAS  Google Scholar 

  • Tabata T, Eaton S, Kornberg TB (1992) The Drosophila hedgehog gene is expressed specifically in posterior compartment cells and is a target of engrailed regulation. Genes Dev 6: 2635–2645

    Article  PubMed  CAS  Google Scholar 

  • Takabatake T, Ogawa M, Takahashi TC, Mizuno M, Okamoto M, Takeshima K (1997) Hedgehog and patched gene expression in adult ocular tissues. FEBS Lett 410: 485–489

    Article  PubMed  CAS  Google Scholar 

  • Tashiro S, Michiue T, Higashijima S, Zenno S, Ishimaru S, Takahashi F, Orihara M, Kojima T, Saigo K (1993) Structure and expression of hedgehog, a Drosophila segment-polarity gene required for cell—cell communication. Gene 124: 183–189

    Article  PubMed  CAS  Google Scholar 

  • Taylor AM, Nakano Y, Mohler J, Ingham PW (1993) Contrasting distributions of patched and hedgehog proteins in the Drosophila embryo. Mech Dev 42: 89–96

    Article  PubMed  CAS  Google Scholar 

  • Theodosiou NA, Zhang S, Wang WY, Xu T (1998) slimb coordinates wg and dpp expression in the dorsal-ventral and anterior-posterior axes during limb development. Development 125: 3411–3416

    Google Scholar 

  • Valentini RP, Brookhiser WT, Park J, Yang T, Briggs J, Dressler G, Holzman LB (1997) Post-translational processing and renal expression of mouse Indian hedgehog. J Biol Chem 272: 8466–8473

    Article  PubMed  CAS  Google Scholar 

  • van den Heuvel M, Ingham PW (1996) smoothened encodes a receptor-like serpentine protein required for hedgehog signalling. Nature 382: 547–551

    Google Scholar 

  • Vorechovsky I, Tingby O, Hartman M, Stromberg B, Nister M, Collins VP, Toftgard R (1997) Somatic mutations in the human homologue of Drosophila patched in primitive neuroectodermal tumours. Oncogene 15: 361–366

    Article  PubMed  CAS  Google Scholar 

  • Vorechovsky I, Unden AB, Sandstedt B, Toftgard R, Stahle-Backdahl M (1997) Trichoepitheliomas contain somatic mutations in the overexpressed PTCH gene: support for a gatekeeper mechanism in skin tumorigenesis. Cancer Res 57: 4677–4681

    PubMed  CAS  Google Scholar 

  • Vortkamp A, Gessler M, Grzeschik KH (1991) GLI3 zinc-finger gene inter- rupted by translocations in Greig syndrome families. Nature 352: 539–540

    Article  PubMed  CAS  Google Scholar 

  • Vortkamp A, Lee K, Lanske B, Segre GV, Kronenberg HM, Tabin CJ (1996) Regulation of rate of cartilage differentiation by Indian hedgehog and PTHrelated protein. Science 273: 613–622

    Article  PubMed  CAS  Google Scholar 

  • Wicking C, Shanley S, Smyth I, Gillies S, Negus K, Graham S, Suthers G, Haites N, Edwards M, Wainwright B, Chenevix-Trench G (1997) 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: 21–26

    PubMed  CAS  Google Scholar 

  • Wild A, Kalff-Suske M, Vortkamp A, Bornholdt D, Konig R, Grzeschik KH (1997) Point mutations in human GLI3 cause Greig syndrome. Hum Mol Genet 6: 1979–1984

    Article  PubMed  CAS  Google Scholar 

  • Wolter M, Reifenberger J, Sommer C, Ruzicka T, Reifenberger G (1997) Mutations in the human homologue 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: 2581–2585

    Google Scholar 

  • Xie J, Johnson RL, Zhang X, Bare JW, Waldman FM, Cogen PH, Menon AG, Warren RS, Chen LC, Scott MP, Epstein E, Jr. (1997) Mutations of the PATCHED gene in several types of sporadic extracutaneous tumors. Cancer Res 57: 2369–2372

    PubMed  CAS  Google Scholar 

  • Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C, Bonifas JM, Lam CW, Hynes M, Goddard A, Rosenthal A, Epstein E Jr, de Sauvage FJ (1998) Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature 391: 90–92

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. E. C. Bailey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. P. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. L. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Abteilung Genetik, Max-Planck-Institut für Entwicklungsbiologie, Spemannstrasse 35/III, 72076, Tübingen, Germany

    Christiane Nüsslein-Volhard

  2. Enabling Technologies, Preclinical Drug Research, Schering AG, Müllerstrasse 178, 13342, Berlin, Germany

    Jörn Krätzschmar

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Bailey, E.C., Scott, M.P., Johnson, R.L. (2000). Hedgehog Signaling in Animal Development and Human Disease. In: Nüsslein-Volhard, C., Krätzschmar, J. (eds) Of Fish, Fly, Worm, and Man. Ernst Schering Research Foundation Workshop, vol 29. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04264-9_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-04264-9_12

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-04266-3

  • Online ISBN: 978-3-662-04264-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation