Gli and hedgehog in cancer: tumours, embryos and stem cells (original) (raw)

• Ackerman, A. B. in Ackermans' Histologic Diagnosis of Neoplastic Skin Diseases: A Method by Pattern Analysis (Ardor Scribendi Publishers, Pennsylvania, 2001).
  Google Scholar
• Ruiz i Altaba, A. Gli proteins and Hedgehog signaling: development and cancer. Trends Genet. 15, 418–425 (1999).
  Article CAS PubMed Google Scholar
• Corcoran, R. B. & Scott, M. P. A mouse model for medulloblastoma and basal cell nevus syndrome. J. Neurooncol. 53, 307–318 (2001).
  Article CAS PubMed Google Scholar
• Wechsler-Reya, R. & Scott, M. P. The developmental biology of brain tumors. Annu. Rev. Neurosci. 24, 385–428 (2001).
  Article CAS PubMed Google Scholar
• Ingham, P. W. & McMahon, A. P. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 15, 3059–3087 (2001).
  Article CAS PubMed Google Scholar
• Ruiz i Altaba, A., Palma, V. & Dahmane, N. Hedgehog–Gli signaling and the growth of the brain. Nature Rev. Neurosci. 3, 24–33 (2002).
  Article CAS Google Scholar
• Felsher, D. W. & Bishop, J. M. Reversible tumorigenesis by MYC in hematopoietic lineages. Mol. Cell 4, 199–207 (1999).
  Article CAS PubMed Google Scholar
• Pelengaris, S., Littlewood, T., Khan, M., Elia, G. & Evan, G. Reversible activation of c-Myc in skin: induction of a complex neoplastic phenotype by a single oncogenic lesion. Mol. Cell 3, 565–577 (1999).
  Article CAS PubMed Google Scholar
• Chin, L. et al. Essential role for oncogenic Ras in tumor maintenance. Nature 400, 468–472 (1999).
  Article CAS PubMed Google Scholar
• Fisher, G. H. et al. Induction and apoptotic regression of lung adenocarcinomas by regulation of a Kras transgene in the presence and absence of tumor suppressor genes. Genes Dev. 15, 3249–3262 (2001).References 7–10 and 12 show that the initiating event is required for tumour maintenance.
  Article CAS PubMed PubMed Central Google Scholar
• Dahmane, N. et al. The Shh–Gli pathway modulates the normal and abnormal growth of the dorsal brain. Development 128, 5201–5212 (2001).Demonstration of a common mechanism for the growth of the neocortex, tectum and cerebellum, and the role of Shh–Gli in various brain tumours, including gliomas.
  Article CAS PubMed Google Scholar
• Jackson, E. L. et al. Analysis of lung tumor initiation and progression using conditional expression of oncogenic Kras. Genes Dev. 15, 3243–3248 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Pathi, S. et al. Comparative biological responses to human Sonic, Indian, and Desert hedgehog. Mech. Dev. 106, 107–117 (2001).
  Article CAS PubMed Google Scholar
• Ruiz i Altaba, A. The works of GLI and the power of hedgehog. Nature Cell Biol. 1, E147–E148 (1999).
  Article CAS PubMed Google Scholar
• Aza-Blanc, P., Ramirez-Weber, F.-A., Laget, M.-P., Schwartz, C. & Kornberg, T. B. Proteolysis that is inhibited by hedgehog targets cubitus interuptus protein to the nucleus and converts it to a repressor. Cell 89, 1043–1053 (1997).Original discovery of repressor function in the Gli family.
  Article CAS PubMed Google Scholar
• Aza-Blanc, P., Lin, H. Y., Ruiz i Altaba, A. & Kornberg, T. B. Expression of the vertebrate Gli proteins in Drosophila reveals a distribution of activator and repressor activities. Development 127, 4293–4301 (2000).Analysis of the vertebrate Gli proteins in transgenic flies confirms the existence of distinct functions for the Gli proteins, and shows that these can have different targets.
  Article PubMed Google Scholar
• Chiang, C. et al. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383, 407–413 (1996).Knockout of Shh in mice.
  CAS PubMed Google Scholar
• Roessler, E. et al. Mutations in the human Sonic Hedgehog gene cause holoprosencephaly. Nature Genet. 14, 357–360 (1996).
  CAS PubMed Google Scholar
• Park, H. L. et al. Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation. Development 127, 1593–1605 (2000).Evidence of Gli1 redundancy in mice.
  Article CAS PubMed Google Scholar
• von Mering, C. & Basler, K. Distinct regulated activities of human Gli proteins in Drosophila. Curr. Biol. 9, 1319–1322 (1999).
  Article CAS PubMed Google Scholar
• Ruiz i Altaba, A. Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic hedgehog. Development 125, 2203–2212 (1998).
  Article PubMed Google Scholar
• Brewster, R, Lee J. & Ruiz i Altaba, A. Gli/Zic factors pattern the neural plate by defining domains of cell differentiation. Nature 393, 579–583 (1998).
  Article CAS PubMed Google Scholar
• Brewster, R., Mullor, J. L. & Ruiz i Altaba, A. Gli2 functions in Fgf signaling during antero-posterior patterning. Development 127, 4395–4405 (2000).Evidence for the regulation of Gli2 and Gli3 by Fgf signalling and their participation in non-hedgehog-dependent events.
  Article PubMed Google Scholar
• Miao, N. et al. Sonic hedgehog promotes the survival of specific CNS neuron populations and protects these cells from toxic insult in vitro. J. Neurosci. 17, 5891–5899 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Ahlgren, S. C. & Bronner-Fraser, M. Inhibition of sonic hedgehog signaling in vivo results in craniofacial neural crest cell death. Curr. Biol. 9, 1304–1314 (1999).
  Article CAS PubMed Google Scholar
• Cobourne, M. T., Hardcastle, Z. & Sharpe, P. T. Sonic hedgehog regulates epithelial proliferation and cell survival in the developing tooth germ. J. Dent. Res. 80, 1974–1979 (2001).
  Article CAS PubMed Google Scholar
• Jessell, T. M. Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nature Rev. Genet. 1, 20–29 (2000).
  Article CAS PubMed Google Scholar
• Dahmane, N. & Ruiz i Altaba, A. Sonic hedgehog regulates the growth and patterning of the cerebellum. Development 126, 3089–3100 (1999).
  Article PubMed Google Scholar
• Wechsler-Reya, R. J. & Scott, M. P. Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron 22, 103–114 (1999).
  Article CAS PubMed Google Scholar
• Wallace, V. A. Purkinje-cell-derived Sonic hedgehog regulates granule neuron precursor cell proliferation in the developing mouse cerebellum. Curr. Biol. 9, 445–448 (1999).References 28–30 discuss the role of Shh in the cerebellar cortex, providing a basis for the action of Purkinje neurons on granule-cell precursors and for the development of medulloblastoma.
  Article CAS PubMed Google Scholar
• Mullor, J. L., Dahmane, N., Sun, T. & Ruiz i Altaba, A. Wnt signals are targets and mediators of Gli function. Curr. Biol. 11, 769–773 (2001).Study of Gli function in mesoderm development and discovery of vertebrate Wnt proteins as targets of Gli proteins.
  Article CAS PubMed Google Scholar
• Kenney, A. M. & Rowitch, D. H. Sonic hedgehog promotes G(1) cyclin expression and sustained cell cycle progression in mammalian neuronal precursors. Mol. Cell Biol. 20, 9055–9067 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Yoon, J. W. et al. Gene expression profiling leads to identification of GLI1 binding elements in target genes and a role for multiple downstream pathways in GLI1 induced cell transformation. J. Biol. Chem. 277, 5548–5555 (2002).
  Article CAS PubMed Google Scholar
• Rowitch, D. H. et al. Sonic hedgehog regulates proliferation and inhibits differentiation of CNS precursor cells. J. Neurosci. 19, 8954–8965 (1999).Study of the effects of Shh misexpression on spinal-cord precursors.
  Article CAS PubMed PubMed Central Google Scholar
• Ericson, J., Morton, S., Kawakami, A., Roelink, H. & Jessell, T. M. Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity. Cell 87, 661–673 (1996).
  Article CAS PubMed Google Scholar
• Barnes, E. A., Kong, M., Ollendorff, V. & Donoghue, D. J. Patched1 interacts with cyclin B1 to regulate cell cycle progression. EMBO J. 20, 2214–2223 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Fan, H. & Khavari, P. A. Sonic hedgehog opposes epithelial cell cycle arrest. J. Cell Biol. 147, 71–76 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Gorlin, R. J. Nevoid basal cell carcinoma syndrome. Dermatol. Clin. 13, 113–125 (1995).
  Article CAS PubMed Google Scholar
• Johnson, R. L. et al. Human homolog of Patched, a candidate gene for basal cell nevus syndrome. Science 272, 1668–1671 (1996).
  Article CAS PubMed Google Scholar
• Hahn, H. et al. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85, 841–851 (1996).References 39 and 40 identify PTCH as the gene that is mutated in Gorlin's or basal-cell nevus syndrome.
  Article CAS PubMed Google Scholar
• Goodrich, L. V., Milenkovic, L., Higgins, K. M. & Scott, M. P. Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277, 1109–1113 (1997).Mouse model for medulloblastoma showing that these tumours develop in mice that lack a copy of Ptc , much like humans with Gorlin's syndrome.
  Article CAS PubMed Google Scholar
• Hahn, H. et al. Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin's syndrome. Nature Med. 4, 619–622 (1998).Demonstration of the development of muscle tumours in Ptc +/− mice and the effects of radiation.
  Article CAS PubMed Google Scholar
• Wetmore, C., Eberhart, D. E. & Curran, T. Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched. Cancer Res. 61, 513–516 (2001).Demonstration that medulloblastomas arise with high frequency in Ptc heterozygotes that lack p53.
  CAS PubMed Google Scholar
• Oro, A. E. et al. Basal cell carcinomas in mice overexpressing sonic hedgehog. Science 276, 817–821 (1997).Development of BCCs in the skin of mouse embryos that misexpress Shh.
  Article CAS PubMed Google Scholar
• Fan, H., Oro, A. E., Scott, M. P. & Khavari, P. A. Induction of basal cell carcinoma features in transgenic human skin expressing Sonic Hedgehog. Nature Med. 3, 788–792 (1997).
  Article CAS PubMed Google Scholar
• Aszterbaum, M. et al. Ultraviolet and ionizing radiation enhance the growth of BCCs and trichoblastomas in patched heterozygous knockout mice. Nature Med. 5, 1285–1291 (1999).Study of the effects of radiation on the development of BCCs in Ptc +/− mice, establishing a model for environmental mutagens and skin cancer.
  Article CAS PubMed Google Scholar
• 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. Nature 389, 876–881 (1997).First evidence for a role of the Gli proteins and the Shh pathway in sporadic BCCs.
  Article CAS PubMed Google Scholar
• Nilsson, M. et al. Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing Gli1. Proc. Natl Acad. Sci. USA 97, 3438–3443 (2000).Development of BCCs in mice that misexpress Gli1 in the skin.
  Article CAS PubMed PubMed Central Google Scholar
• Grachtchouk, M. et al. Basal cell carcinomas in mice overexpressing Gli2 in skin. Nature Genet. 24, 216–217 (2000).Development of basal-cell carcinomas in mice through the misexpression of Gli2 in the epidermis.
  Article CAS PubMed Google Scholar
• Gailani, M. R. et al. The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nature Genet. 14, 78–81 (1996).
  Article CAS PubMed Google Scholar
• Unden, A. B., Zaphiropoulos, P. G., Bruce, K., Toftgard, R. & Stahle-Backdahl, M. Human patched (PTCH) mRNA is overexpressed consistently in tumor cells of both familial and sporadic basal cell carcinoma. Cancer Res. 57, 2336–2340 (1997).
  CAS PubMed Google Scholar
• Kalhassy, M. et al. Patched (PTCH)-associated preferential expression of smoothened (SMOH) in human basal cell carcinoma of the skin. Cancer Res. 57, 4731–4735 (1997).
  Google Scholar
• Wolter, M., Reifenberger, J., Sommer, C., Ruzicka, T. & Reifenberger, G. 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 (1997).
  CAS PubMed Google Scholar
• Xie, J. et al. Mutations of the PATCHED gene in several types of sporadic extracutaneous tumors. Cancer Res. 57, 2369–2372 (1997).
  CAS PubMed Google Scholar
• Xie, J. et al. Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature 391, 90–92 (1998).Shows the potency of activated Smo mutants in instigating the Shh pathway.
  Article CAS PubMed Google Scholar
• Reifenberger, J. et al. 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 (1998).
  CAS PubMed Google Scholar
• Ghali, L., Wong, S. T., Green, J., Tidman, N. & Quinn, A. G. Gli1 protein is expressed in basal cell carcinomas, outer root sheath keratinocytes and a subpopulation of mesenchymal cells in normal human skin. J. Invest. Dermatol. 113, 595–599 (1999).
  Article CAS PubMed Google Scholar
• Bonifas, J. M. et al. Activation of expression of hedgehog target genes in basal cell carcinomas. J. Invest. Dermatol. 116, 739–742 (2001).
  Article CAS PubMed Google Scholar
• Stein, U. et al. GLI gene expression in bone and soft tissue sarcomas of adult patients correlates with tumor grade. Cancer Res. 59, 1890–1895 (1999).
  CAS PubMed Google Scholar
• Kimonis, V. E. et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am. J. Med. Genet. 69, 299–308 (1997).
  Article CAS PubMed Google Scholar
• Callahan, C. A. & Oro, A. E. Monstrous attempts at adnexogenesis: regulating hair follicle progenitors through Sonic hedgehog signaling. Curr. Opin. Genet. Dev. 11, 541–546 (2001).
  Article CAS PubMed Google Scholar
• St-Jacques, B. et al. Sonic hedgehog signaling is essential for hair development. Curr. Biol. 8, 1058–1068 (1998).
  Article CAS PubMed Google Scholar
• Chiang, C. et al. Essential role for Sonic hedgehog during hair follicle morphogenesis. Dev. Biol. 205, 1–9 (1999).
  Article CAS PubMed Google Scholar
• Sato, N., Leopold, P. L. & Crystal, R. G. Induction of the hair growth phase in postnatal mice by localized transient expression of Sonic hedgehog. J. Clin. Invest. 104, 855–864 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Karlsson, L., Bondjers, C. & Betsholtz, C. Roles for PDGF-A and sonic hedgehog in development of mesenchymal components of the hair follicle. Development 126, 2611–2621 (1999).
  Article CAS PubMed Google Scholar
• Taylor, G., Lehrer, M. S., Jensen, P. J., Sun, T.-T. & Lavker, R. M. Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell 102, 451–461 (2000).Study of the potential of stem cells in the bulge region of the hair follicle.
  Article CAS PubMed Google Scholar
• Fuchs, E., Merrill, B. J., Jamora, C. & DasGupta, R. At the roots of a never-ending cycle. Dev. Cell 1, 13–25 (2001).
  Article CAS PubMed Google Scholar
• Marino, S., Vooijs, M., van Der Gulden, H., Jonkers, J. & Berns, A. Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum. Genes Dev. 14, 994–1004 (2000).Unexpected development of medulloblastomas from lack of Trp53 and Rb in granule-cell precursors.
  Article CAS PubMed PubMed Central Google Scholar
• Gao, W. O., Heintz, N. & Hatten, M. E. Cerebellar granule cell neurogenesis is regulated by cell–cell interactions. Neuron 6, 705–715 (1991).
  Article CAS PubMed Google Scholar
• Raffel, C. et al. Sporadic medulloblastomas contain PTCH mutations. Cancer Res. 57, 842–845 (1997).
  CAS PubMed Google Scholar
• Pietsch, T. et al. Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched. Cancer Res. 57, 2085–2088 (1997).
  CAS PubMed Google Scholar
• Vortmeyer, A. O. et al. Deletion analysis of the adenomatous polyposis coli and PTCH gene loci in patients with sporadic and nevoid basal cell carcinoma syndrome-associated medulloblastoma. Cancer 85, 2662–2667 (1999).
  Article CAS PubMed Google Scholar
• Zurawel, R. H. et al. Analysis of PTCH/SMO/SHH pathway genes in medulloblastoma. Genes Chromosom. Cancer 27, 44–51 (2000).
  Article CAS PubMed Google Scholar
• Pomeroy, S. L. et al. Prediction of central nervous system embryonal tumor outcome based on gene expression. Nature 415, 436–442 (2002).
  Article CAS PubMed Google Scholar
• Holland, E. C. Gliomagenesis: genetic alterations and mouse models. Nature Rev. Genet. 2, 120–129 (2001).
  Article CAS PubMed Google Scholar
• Maher, E. A. et al. Malignant glioma: genetics and biology of a grave matter. Genes Dev. 15, 1311–1333 (2001).
  Article CAS PubMed Google Scholar
• Kleihues, P. & Cavenee, W. K. Tumors of the Nervous System (International Agency for Research on Cancer, Lyon, 1997).
  Google Scholar
• Nishikawa, R. et al. A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc. Natl Acad. Sci. USA 91, 7727–7731 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Uhrbom, L., Hesselager, G., Nister, M. & Westermark, B. Induction of brain tumors in mice using a recombinant platelet-derived growth factor B-chain retrovirus. Cancer Res. 58, 5275–5279 (1998).Ability of Pdgf signalling to induce brain tumorigenesis.
  CAS PubMed Google Scholar
• Holland, E. C. et al. Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nature Genet. 25, 55–57 (2000).
  Article CAS PubMed Google Scholar
• Dai, C. et al. PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev. 15, 1913–1925 (2001).Study of the ability of the Pdgf pathway to initiate gliomagenesis in mice.
  Article CAS PubMed PubMed Central Google Scholar
• Ding, H. et al. Astrocyte-specific expression of activated p21-ras results in malignant astrocytoma formation in a transgenic mouse model of human gliomas. Cancer Res. 61, 3826–3836 (2001).
  CAS PubMed Google Scholar
• Kinzler, K. W. et al. Identification of an amplified, highly expressed gene in a human glioma. Science 236, 70–73 (1987).Original isolation and identification of Gli1.
  Article CAS PubMed Google Scholar
• Salgaller, M., Pearl, D. & Stephens, R. In situ hybridization with single-stranded RNA probes to demonstrate infrequently elevated Gli mRNA and no increased Ras mRNA levels in meningiomas and astrocytomas. Cancer Lett. 57, 243–253 (1991).
  Article CAS PubMed Google Scholar
• Xiao, H., Goldthwait, D. A. & Mapstone, T. A search for Gli expression in tumors of the central nervous system. Pediatr. Neurosurg. 20, 178–182 (1994).
  Article CAS PubMed Google Scholar
• Millen, K. J., Hui, C.-C. & Joyner, A. L. A role for En-2 and other murine homologues of Drosophila segment polarity genes in regulating positional information in the developing cerebellum. Development 121, 3935–3945 (1995).
  Article CAS PubMed Google Scholar
• Incardona, J. P., Gaffield, W., Kapur, R. P. & Roelink, H. The teratogenic Veratrum alkaloid cyclopamine inhibits sonic hedgehog signal transduction. Development 125, 3553–3562 (1998).
  Article CAS PubMed Google Scholar
• Cooper, M. K., Porter, J. A., Young, K. E. & Beachy, P. A. Teratogen-mediated inhibition of target tissue response to Shh signaling. Science 280, 1603–1607 (1998).References 87 and 88 discuss the site of action of cyclopamine in the inhibition of Shh signalling.
  Article CAS PubMed Google Scholar
• Taipale, J. et al. Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine. Nature 406, 1005–1009 (2000).Detailed study of the effects of cyclopamine on the Shh receptor complex.
  Article CAS PubMed Google Scholar
• Van Tuyl, M. & Post, M. From fruitflies to mammals: mechanisms of signaling via the Sonic hedgehog pathway in lung development. Resp. Res. 1, 30–35 (2001).
  Article Google Scholar
• Miller, L. A., Wert, S. E. & Whitsett, J. A. Immunolocalization of sonic hedgehog (shh) in developing mouse lung. J. Histochem. Cytochem. 49, 1593–1604 (2001).
  Article CAS PubMed Google Scholar
• Podlasek, C. A., Barnett, D. H., Clemens, J. Q., Bak, P. M. & Bushman, W. Prostate development requires Sonic hedgehog expressed by the urogenital sinus epithelium. Dev. Biol. 209, 28–39 (1999).
  Article CAS PubMed Google Scholar
• Abate-Shen, C. & Shen, M. M. Molecular genetics of prostate cancer. Genes Dev. 14, 2410–2434 (2000).
  Article CAS PubMed Google Scholar
• Levanat, S., Pavelic, B., Crnic, I., Oreskovic, S. & Manojlovic, S. Involvement of PTCH gene in various noninflammatory cysts. J. Mol. Med. 78, 140–146 (2000).
  Article CAS PubMed Google Scholar
• Kwan, H. et al. Transgenes expressing the Wnt1 and Wnt2 proto-oncogenes cooperate during mammary carcinogenesis in doubly transgenic mice. Mol. Cell. Biol. 12, 147–154 (1992).
  CAS PubMed PubMed Central Google Scholar
• Shackleford, G. M., MacArthur, C. A., Kwan, H. C. & Varmus, H. E. Mouse mammary tumor virus infection accelerates mammary carcinogenesis in Wnt1 transgenic mice by insertional activation of Wnt2/Fgf3 and Hst/Fgf4. Proc. Natl Acad. Sci. USA 90, 740–744 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Lewis, M. T. Hedgehog signalling in mouse mammary gland development and neoplasia. J. Mammary Gland Biol. Neoplasia 6, 53–66 (2001).
  Article CAS PubMed Google Scholar
• Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57–70 (2000).
  Article CAS PubMed Google Scholar
• Wetmore, C., Eberhart, D. E. & Curran, T. The normal patched allele is expressed in medulloblastomas from mice with heterozygous germ-line mutation of patched. Cancer Res. 60, 2239–2246 (2000).
  CAS PubMed Google Scholar
• Krishnan, V. et al. Mediation of Sonic hedgehog-induced expression of COUP-TFII by a protein phosphatase. Science 278, 1947–1950 (1997).
  Article CAS PubMed Google Scholar
• Apidianakis, Y., Grbavec, D., Stifani, S. & Delidakis, C. Groucho mediates a Ci-independent mechanism of hedgehog repression in the anterior wing pouch. Development 128, 4361–4370 (2001).
  Article CAS PubMed Google Scholar
• Ruppert, J. M., Vogelstein, B. & Kinzler, K. W. The zinc finger protein GLI transforms primary cells in cooperation with adenovirus E1A. Mol. Cell. Biol. 11, 1724–1728 (1991).
  CAS PubMed PubMed Central Google Scholar
• Kato, M. et al. Identification of sonic hedgehog-responsive genes using cDNA microarray. Biochem. Biophys. Res. Commun. 289, 472–478 (2001).
  Article CAS PubMed Google Scholar
• Malik, K. & Brown, K. W. Epigenetic gene deregulation in cancer. Br. J. Cancer 83, 1583–1588 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Bergstein, I. When is precancerous actually postcancerous? Mol. Carcinog. 29, 129–133 (2000).
  Article CAS PubMed Google Scholar
• Reya, T., Morrison, S. J., Clarke, M. F. & Weissman, I. L. Stem cells, cancer, and cancer stem cells. Nature 414, 105–111 (2001).
  Article CAS PubMed Google Scholar
• Bonnet, D. & Dick, J. E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Med. 3, 730–737 (1997).
  Article CAS PubMed Google Scholar
• Bhardwaj, G. et al. Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nature Immunol. 2, 172–180 (2001).Study of the role of the Shh pathway in the haematopoietic system.
  Article CAS Google Scholar
• Detmer, K., Walker, A. N., Jenkins, T. M., Steele, T. A. & Dannawi, H. Erythroid differentiation in vitro is blocked by cyclopamine, an inhibitor of hedgehog signaling. Blood Cells Mol. Dis. 26, 360–372 (2000).
  Article CAS PubMed Google Scholar
• Biernat, W. et al. Identical mutations of the p53 tumor suppressor gene in the gliomatous and the sarcomatous component soft gliosarcomas suggest a common origin from glial cells. J. Neuropathol. Exp. Neurol. 54, 651–656 (1995).
  Article CAS PubMed Google Scholar
• Boerman, R. H. et al. The glial and mesenchymal elements of gliosarcomas share similar genetic alterations. J. Neuropathol. Exp. Neurol. 55, 973–981 (1996).
  Article CAS PubMed Google Scholar
• Mueller, W. et al. Clonal analysis in glioblastoma with epithelial differentiation. Brain Pathol. 11, 39–43 (2001).
  Article CAS PubMed Google Scholar
• Reis, R. M., Konu-Lebleblicioglu, D., Lopes, J. M., Kleihues, P. & Ohgaki, H. Genetic profile of gliosarcomas. Am. J. Pathol. 156, 425–432 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Dassule, H. R., Lewis, P., Bei, M., Maas, R. & McMahon, A. P. Sonic hedgehog regulates growth and morphogenesis of the tooth. Development 127, 4775–4785 (2000).
  Article CAS PubMed Google Scholar
• Mintz, B. & Fleischman, R. A. Teratocarcinomas and other neoplasms as developmental defects in gene expression. Adv. Cancer Res. 34, 211–278 (1981).
  Article CAS PubMed Google Scholar
• Cano, A. et al. The transcription factor snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression. Nature Cell Biol. 2, 76–83 (2000).Study of the role of Snail family genes in cell shape and position changes in development and cancer.
  Article CAS PubMed Google Scholar
• Lu, Q. R. et al. Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain tumors. Proc. Natl Acad. Sci. USA 98, 10851–10856 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Morin, P. J. et al. Activation of β-catenin–TCF signaling in colon cancer by mutations in β-catenin or APC. Science 275, 1787–1790 (1997).
  Article CAS PubMed Google Scholar
• Korinek, V. et al. Constitutive transcriptional activation by a β-catenin–TCF complex in APC −/− colon carcinoma. Science 275, 1784–1787 (1997).
  Article CAS PubMed Google Scholar
• Polakis, P. Wnt signaling and cancer. Genes Dev. 14, 1837–1851 (2000).
  Article CAS PubMed Google Scholar
• Alvarez-Buylla, A., Garcia-Verdugo, J. M. & Tramontin, A. D. A unified hypothesis on the lineage of neural stem cells. Nature Rev. Neurosci. 2, 287–293 (2001).
  Article CAS Google Scholar
• Brockes, J. P. Amphibian limb regeneration: rebuilding a complex structure. Science 276, 81–87 (1997).
  Article CAS PubMed Google Scholar
• Kalyani, A., Hobson, K. & Rao, M. S. Neuroepithelial stem cells from the embryonic spinal cord: isolation, characterization, and clonal analysis. Dev. Biol. 186, 202–223 (1997).
  Article CAS PubMed Google Scholar
• Groszer, M. et al. Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo. Science 294, 2186–2189 (2001).Genetic analysis of PTEN function, revealing an unsuspected role in the control of progenitor-cell numbers.
  Article CAS PubMed Google Scholar
• MacDonald, T. J. et al. Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nature Genet. 29, 143–152 (2001).
  Article CAS PubMed Google Scholar
• Xie, J. et al. A role of PDGFRα in basal cell carcinoma proliferation. Proc. Natl Acad. Sci. USA 98, 9255–9259 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Uhrbom, L., Hesselager, G., Ostman, A., Nister, M. & Westermark, B. Dependence of autocrine growth factor stimulation in platelet-derived growth factor-B-induced mouse brain tumor cells. Int. J. Cancer 85, 398–406 (2000).
  Article CAS PubMed Google Scholar
• Trojan, J., Johnson, T. R., Rudin, S. D., Ilan, J. & Tykocinski, M. L. Treatment and prevention of rat glioblastoma by immunogenic C6 cells expressing antisense insulin-like growth factor 1 RNA. Science 259, 94–97 (1993).
  Article CAS PubMed Google Scholar
• Zumkeller, W. & Westphal, M. The IGF/IGFBP system in CNS malignancy. Mol. Pathol. 54, 227–229 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Hahn, H. et al. Patched target Igf2 is indispensable for the formation of medulloblastoma and rhabdomyosarcoma. J. Biol. Chem. 275, 28341–28344 (2000).Identification of the Igf signalling pathway as a target of Shh–Gli function.
  CAS PubMed Google Scholar
• Koch, A. et al. Somatic mutations of WNT/wingless signaling pathway components in primitive neuroectodermal tumors. Int. J. Cancer 93, 445–449 (2001).
  Article CAS PubMed Google Scholar
• Ellisen, L. W. et al. TAN1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66, 649–661 (1991).
  Article CAS PubMed Google Scholar
• Pear, W. S. et al. Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles. J. Exp. Med. 183, 2283–2291 (1996).
  Article CAS PubMed Google Scholar
• Karanu, F. N. et al. The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells. J. Exp. Med. 192, 1365–1372 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Varnum-Finney, B. et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nature Med. 6, 1278–1281 (2000).
  Article CAS PubMed Google Scholar
• Gaiano, N., Nye, J. S. & Fishell, G. Radial glia identity is promoted by Notch 1 signaling in the murine forebrain. Neuron 26, 395–404 (2000).
  Article CAS PubMed Google Scholar
• Solecki, D. J., Liu, X. L., Tomoda, T., Fang, Y. & Hatten, M. E. Activated Notch2 signaling inhibits differentiation of cerebellar granule neuron precursors by maintaining proliferation. Neuron 31, 557–568 (2001).Involvement of Notch signalling in the process of granule-neuron precursor proliferation. An interesting potential link with Shh signalling.
  Article CAS PubMed Google Scholar