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Erschienen in: The Cerebellum 3/2009

01.09.2009

SHH Pathway and Cerebellar Development

verfasst von: Catherine Vaillant, Denis Monard

Erschienen in: The Cerebellum | Ausgabe 3/2009

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Abstract

The morphogenetic factor Sonic hedgehog (SHH) has been discovered as one of the masterplayers in cerebellar patterning and was subjected to intensive investigation during the last decade. During early postnatal development, this continuously secreted cholesterol-modified protein drives the expansion of the largest neuronal population of the brain, the granular cells. Moreover, it acts on Bergmann glia differentiation and would potentially affect Purkinje cells homeostasis at adult age. The cerebellar cortex constituted an ideal developmental model to dissect out the upstream mechanisms and downstream targets of this complex pathway. Its deep understanding discloses some of the mechanistic disorders underlying pediatric tumorigenesis, congenital ataxia, and mental retardation. Therapeutical use of its regulators has been consolidated on murine transgenic models and is now considered as a realistic human clinical application. Here, we will review the most recent advances made in the comprehensive understanding of SHH involvement in cerebellar development and pathology.
Literatur
1.
Zurück zum Zitat McMahon AP, Ingham PW, Tabin CJ (2003) Developmental roles and clinical significance of hedgehog signaling. Curr Top Dev Biol 53:1–114PubMedCrossRef McMahon AP, Ingham PW, Tabin CJ (2003) Developmental roles and clinical significance of hedgehog signaling. Curr Top Dev Biol 53:1–114PubMedCrossRef
2.
3.
Zurück zum Zitat DeCamp DL, Thompson TM, de Sauvage FJ, Lerner MR (2000) Smoothened activates Galphai-mediated signaling in frog melanophores. J Biol Chem 275:26322–26327PubMedCrossRef DeCamp DL, Thompson TM, de Sauvage FJ, Lerner MR (2000) Smoothened activates Galphai-mediated signaling in frog melanophores. J Biol Chem 275:26322–26327PubMedCrossRef
4.
Zurück zum Zitat Huangfu D, Anderson KV (2006) Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates. Development 133:3–14PubMedCrossRef Huangfu D, Anderson KV (2006) Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates. Development 133:3–14PubMedCrossRef
5.
Zurück zum Zitat Fuccillo M, Joyner AL, Fishell G (2006) Morphogen to mitogen: the multiple roles of hedgehog signalling in vertebrate neural development. Nat Rev Neurosci 7:772–783PubMedCrossRef Fuccillo M, Joyner AL, Fishell G (2006) Morphogen to mitogen: the multiple roles of hedgehog signalling in vertebrate neural development. Nat Rev Neurosci 7:772–783PubMedCrossRef
6.
Zurück zum Zitat Sillitoe RV, Joyner AL (2007) Morphology, molecular codes, and circuitry produce the three-dimensional complexity of the cerebellum. Annu Rev Cell Dev Biol 23:549–577PubMedCrossRef Sillitoe RV, Joyner AL (2007) Morphology, molecular codes, and circuitry produce the three-dimensional complexity of the cerebellum. Annu Rev Cell Dev Biol 23:549–577PubMedCrossRef
7.
Zurück zum Zitat Hatten ME, Alder J, Zimmerman K, Heintz N (1997) Genes involved in cerebellar cell specification and differentiation. Curr Opin Neurobiol 7:40–47PubMedCrossRef Hatten ME, Alder J, Zimmerman K, Heintz N (1997) Genes involved in cerebellar cell specification and differentiation. Curr Opin Neurobiol 7:40–47PubMedCrossRef
8.
Zurück zum Zitat Repetto M, Maziere JC, Citadelle D, Dupuis R, Meier M, Biade S et al (1990) Teratogenic effect of the cholesterol synthesis inhibitor AY 9944 on rat embryos in vitro. Teratology 42:611–618PubMedCrossRef Repetto M, Maziere JC, Citadelle D, Dupuis R, Meier M, Biade S et al (1990) Teratogenic effect of the cholesterol synthesis inhibitor AY 9944 on rat embryos in vitro. Teratology 42:611–618PubMedCrossRef
9.
Zurück zum Zitat Lanoue L, Dehart DB, Hinsdale ME, Maeda N, Tint GS, Sulik KK (1997) Limb, genital, CNS, and facial malformations result from gene/environment-induced cholesterol deficiency: further evidence for a link to sonic hedgehog. Am J Med Genet 73:24–31PubMedCrossRef Lanoue L, Dehart DB, Hinsdale ME, Maeda N, Tint GS, Sulik KK (1997) Limb, genital, CNS, and facial malformations result from gene/environment-induced cholesterol deficiency: further evidence for a link to sonic hedgehog. Am J Med Genet 73:24–31PubMedCrossRef
10.
Zurück zum Zitat Dehart DB, Lanoue L, Tint GS, Sulik KK (1997) Pathogenesis of malformations in a rodent model for Smith–Lemli–Opitz syndrome. Am J Med Genet 68:328–337PubMedCrossRef Dehart DB, Lanoue L, Tint GS, Sulik KK (1997) Pathogenesis of malformations in a rodent model for Smith–Lemli–Opitz syndrome. Am J Med Genet 68:328–337PubMedCrossRef
11.
Zurück zum Zitat Yu H, Patel SB (2005) Recent insights into the Smith–Lemli–Opitz syndrome. Clin Genet 68:383–391PubMedCrossRef Yu H, Patel SB (2005) Recent insights into the Smith–Lemli–Opitz syndrome. Clin Genet 68:383–391PubMedCrossRef
12.
Zurück zum Zitat Porter FD (2003) Human malformation syndromes due to inborn errors of cholesterol synthesis. Curr Opin Pediatr 15:607–613PubMedCrossRef Porter FD (2003) Human malformation syndromes due to inborn errors of cholesterol synthesis. Curr Opin Pediatr 15:607–613PubMedCrossRef
13.
Zurück zum Zitat Dahmane N, Ruiz i Altaba A (1999) Sonic hedgehog regulates the growth and patterning of the cerebellum. Development 126:3089–3100PubMed Dahmane N, Ruiz i Altaba A (1999) Sonic hedgehog regulates the growth and patterning of the cerebellum. Development 126:3089–3100PubMed
14.
Zurück zum Zitat Wallace VA (1999) Purkinje-cell-derived Sonic hedgehog regulates granule neuron precursor cell proliferation in the developing mouse cerebellum. Curr Biol 9:445–448PubMedCrossRef Wallace VA (1999) Purkinje-cell-derived Sonic hedgehog regulates granule neuron precursor cell proliferation in the developing mouse cerebellum. Curr Biol 9:445–448PubMedCrossRef
15.
Zurück zum Zitat Wechsler-Reya RJ, Scott MP (1999) Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron 22:103–114PubMedCrossRef Wechsler-Reya RJ, Scott MP (1999) Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron 22:103–114PubMedCrossRef
16.
Zurück zum Zitat Kenney AM, Rowitch DH (2000) Sonic hedgehog promotes G(1) cyclin expression and sustained cell cycle progression in mammalian neuronal precursors. Mol Cell Biol 20:9055–9067PubMedCrossRef Kenney AM, Rowitch DH (2000) Sonic hedgehog promotes G(1) cyclin expression and sustained cell cycle progression in mammalian neuronal precursors. Mol Cell Biol 20:9055–9067PubMedCrossRef
17.
Zurück zum Zitat Corrales JD, Blaess S, Mahoney EM, Joyner AL (2006) The level of sonic hedgehog signaling regulates the complexity of cerebellar foliation. Development 133:1811–1821PubMedCrossRef Corrales JD, Blaess S, Mahoney EM, Joyner AL (2006) The level of sonic hedgehog signaling regulates the complexity of cerebellar foliation. Development 133:1811–1821PubMedCrossRef
18.
Zurück zum Zitat Corrales JD, Rocco GL, Blaess S, Guo Q, Joyner AL (2004) Spatial pattern of sonic hedgehog signaling through Gli genes during cerebellum development. Development 131:5581–5590PubMedCrossRef Corrales JD, Rocco GL, Blaess S, Guo Q, Joyner AL (2004) Spatial pattern of sonic hedgehog signaling through Gli genes during cerebellum development. Development 131:5581–5590PubMedCrossRef
19.
Zurück zum Zitat Traiffort E, Charytoniuk D, Watroba L, Faure H, Sales N, Ruat M (1999) Discrete localizations of hedgehog signalling components in the developing and adult rat nervous system. Eur J Neurosci 11:3199–31214PubMedCrossRef Traiffort E, Charytoniuk D, Watroba L, Faure H, Sales N, Ruat M (1999) Discrete localizations of hedgehog signalling components in the developing and adult rat nervous system. Eur J Neurosci 11:3199–31214PubMedCrossRef
20.
Zurück zum Zitat Lewis PM, Gritli-Linde A, Smeyne R, Kottmann A, McMahon AP (2004) Sonic hedgehog signaling is required for expansion of granule neuron precursors and patterning of the mouse cerebellum. Dev Biol 270:393–410PubMedCrossRef Lewis PM, Gritli-Linde A, Smeyne R, Kottmann A, McMahon AP (2004) Sonic hedgehog signaling is required for expansion of granule neuron precursors and patterning of the mouse cerebellum. Dev Biol 270:393–410PubMedCrossRef
21.
Zurück zum Zitat Diaz E, Ge Y, Yang YH, Loh KC, Serafini TA, Okazaki Y et al (2002) Molecular analysis of gene expression in the developing pontocerebellar projection system. Neuron 36:417–434PubMedCrossRef Diaz E, Ge Y, Yang YH, Loh KC, Serafini TA, Okazaki Y et al (2002) Molecular analysis of gene expression in the developing pontocerebellar projection system. Neuron 36:417–434PubMedCrossRef
22.
Zurück zum Zitat Oliver TG, Grasfeder LL, Carroll AL, Kaiser C, Gillingham CL, Lin SM et al (2003) Transcriptional profiling of the Sonic hedgehog response: a critical role for N-myc in proliferation of neuronal precursors. Proc Natl Acad Sci U S A 100:7331–7336PubMedCrossRef Oliver TG, Grasfeder LL, Carroll AL, Kaiser C, Gillingham CL, Lin SM et al (2003) Transcriptional profiling of the Sonic hedgehog response: a critical role for N-myc in proliferation of neuronal precursors. Proc Natl Acad Sci U S A 100:7331–7336PubMedCrossRef
23.
Zurück zum Zitat Sjostrom SK, Finn G, Hahn WC, Rowitch DH, Kenney AM (2005) The Cdk1 complex plays a prime role in regulating N-myc phosphorylation and turnover in neural precursors. Dev Cell 9:327–338PubMedCrossRef Sjostrom SK, Finn G, Hahn WC, Rowitch DH, Kenney AM (2005) The Cdk1 complex plays a prime role in regulating N-myc phosphorylation and turnover in neural precursors. Dev Cell 9:327–338PubMedCrossRef
24.
Zurück zum Zitat Zhao Q, Kho A, Kenney AM, Yuk Di DI, Kohane I, Rowitch DH (2002) Identification of genes expressed with temporal-spatial restriction to developing cerebellar neuron precursors by a functional genomic approach. Proc Natl Acad Sci U S A 99:5704–5709PubMedCrossRef Zhao Q, Kho A, Kenney AM, Yuk Di DI, Kohane I, Rowitch DH (2002) Identification of genes expressed with temporal-spatial restriction to developing cerebellar neuron precursors by a functional genomic approach. Proc Natl Acad Sci U S A 99:5704–5709PubMedCrossRef
25.
Zurück zum Zitat Pogoriler J, Millen K, Utset M, Du W (2006) Loss of cyclin D1 impairs cerebellar development and suppresses medulloblastoma formation. Development 133:3929–3937PubMedCrossRef Pogoriler J, Millen K, Utset M, Du W (2006) Loss of cyclin D1 impairs cerebellar development and suppresses medulloblastoma formation. Development 133:3929–3937PubMedCrossRef
26.
Zurück zum Zitat Huard JM, Forster CC, Carter ML, Sicinski P, Ross ME (1999) Cerebellar histogenesis is disturbed in mice lacking cyclin D2. Development 126:1927–1935PubMed Huard JM, Forster CC, Carter ML, Sicinski P, Ross ME (1999) Cerebellar histogenesis is disturbed in mice lacking cyclin D2. Development 126:1927–1935PubMed
27.
Zurück zum Zitat Ciemerych MA, Kenney AM, Sicinska E, Kalaszczynska I, Bronson RT, Rowitch DH et al (2002) Development of mice expressing a single D-type cyclin. Genes Dev 16:3277–3289PubMedCrossRef Ciemerych MA, Kenney AM, Sicinska E, Kalaszczynska I, Bronson RT, Rowitch DH et al (2002) Development of mice expressing a single D-type cyclin. Genes Dev 16:3277–3289PubMedCrossRef
28.
Zurück zum Zitat Schuller U, Zhao Q, Godinho SA, Heine VM, Medema RH, Pellman D et al (2007) Forkhead transcription factor FoxM1 regulates mitotic entry and prevents spindle defects in cerebellar granule neuron precursors. Mol Cell Biol 27:8259–8270PubMedCrossRef Schuller U, Zhao Q, Godinho SA, Heine VM, Medema RH, Pellman D et al (2007) Forkhead transcription factor FoxM1 regulates mitotic entry and prevents spindle defects in cerebellar granule neuron precursors. Mol Cell Biol 27:8259–8270PubMedCrossRef
29.
Zurück zum Zitat Knoepfler PS, Cheng PF, Eisenman RN (2002) N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes Dev 16:2699–2712PubMedCrossRef Knoepfler PS, Cheng PF, Eisenman RN (2002) N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes Dev 16:2699–2712PubMedCrossRef
30.
Zurück zum Zitat Kenney AM, Cole MD, Rowitch DH (2003) Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors. Development 130:15–28PubMedCrossRef Kenney AM, Cole MD, Rowitch DH (2003) Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors. Development 130:15–28PubMedCrossRef
31.
Zurück zum Zitat Yun JS, Rust JM, Ishimaru T, Diaz E (2007) A novel role of the Mad family member Mad3 in cerebellar granule neuron precursor proliferation. Mol Cell Biol 27:8178–8189PubMedCrossRef Yun JS, Rust JM, Ishimaru T, Diaz E (2007) A novel role of the Mad family member Mad3 in cerebellar granule neuron precursor proliferation. Mol Cell Biol 27:8178–8189PubMedCrossRef
32.
Zurück zum Zitat Leung C, Lingbeek M, Shakhova O, Liu J, Tanger E, Saremaslani P et al (2004) Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature 428:337–341PubMedCrossRef Leung C, Lingbeek M, Shakhova O, Liu J, Tanger E, Saremaslani P et al (2004) Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature 428:337–341PubMedCrossRef
33.
Zurück zum Zitat Traiffort E, Charytoniuk DA, Faure H, Ruat M (1998) Regional distribution of Sonic Hedgehog, patched, and smoothened mRNA in the adult rat brain. J Neurochem 70:1327–1330PubMedCrossRef Traiffort E, Charytoniuk DA, Faure H, Ruat M (1998) Regional distribution of Sonic Hedgehog, patched, and smoothened mRNA in the adult rat brain. J Neurochem 70:1327–1330PubMedCrossRef
34.
Zurück zum Zitat Klein RS, Rubin JB, Gibson HD, DeHaan EN, Alvarez-Hernandez X, Segal RA et al (2001) SDF-1 alpha induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells. Development 128:1971–1981PubMed Klein RS, Rubin JB, Gibson HD, DeHaan EN, Alvarez-Hernandez X, Segal RA et al (2001) SDF-1 alpha induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells. Development 128:1971–1981PubMed
35.
Zurück zum Zitat Hartmann W, Koch A, Brune H, Waha A, Schuller U, Dani I et al (2005) Insulin-like growth factor II is involved in the proliferation control of medulloblastoma and its cerebellar precursor cells. Am J Pathol 166:1153–1162PubMed Hartmann W, Koch A, Brune H, Waha A, Schuller U, Dani I et al (2005) Insulin-like growth factor II is involved in the proliferation control of medulloblastoma and its cerebellar precursor cells. Am J Pathol 166:1153–1162PubMed
36.
Zurück zum Zitat Parathath SR, Mainwaring LA, Fernandez LA, Campbell DO, Kenney AM (2008) Insulin receptor substrate 1 is an effector of sonic hedgehog mitogenic signaling in cerebellar neural precursors. Development 135(19):3291–3300PubMedCrossRef Parathath SR, Mainwaring LA, Fernandez LA, Campbell DO, Kenney AM (2008) Insulin receptor substrate 1 is an effector of sonic hedgehog mitogenic signaling in cerebellar neural precursors. Development 135(19):3291–3300PubMedCrossRef
37.
Zurück zum Zitat Shah OJ, Hunter T (2006) Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis. Mol Cell Biol 26:6425–6434PubMedCrossRef Shah OJ, Hunter T (2006) Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis. Mol Cell Biol 26:6425–6434PubMedCrossRef
38.
Zurück zum Zitat Vaillant C, Didier-Bazes M, Hutter A, Belin MF, Thomasset N (1999) Spatiotemporal expression patterns of metalloproteinases and their inhibitors in the postnatal developing rat cerebellum. J Neurosci 19:4994–5004PubMed Vaillant C, Didier-Bazes M, Hutter A, Belin MF, Thomasset N (1999) Spatiotemporal expression patterns of metalloproteinases and their inhibitors in the postnatal developing rat cerebellum. J Neurosci 19:4994–5004PubMed
39.
Zurück zum Zitat Vaillant C, Meissirel C, Mutin M, Belin MF, Lund LR, Thomasset N (2003) MMP-9 deficiency affects axonal outgrowth, migration, and apoptosis in the developing cerebellum. Mol Cell Neurosci 24:395–408PubMedCrossRef Vaillant C, Meissirel C, Mutin M, Belin MF, Lund LR, Thomasset N (2003) MMP-9 deficiency affects axonal outgrowth, migration, and apoptosis in the developing cerebellum. Mol Cell Neurosci 24:395–408PubMedCrossRef
40.
Zurück zum Zitat Blaess S, Graus-Porta D, Belvindrah R, Radakovits R, Pons S, Littlewood-Evans A et al (2004) Beta1-integrins are critical for cerebellar granule cell precursor proliferation. J Neurosci 24:3402–3412PubMedCrossRef Blaess S, Graus-Porta D, Belvindrah R, Radakovits R, Pons S, Littlewood-Evans A et al (2004) Beta1-integrins are critical for cerebellar granule cell precursor proliferation. J Neurosci 24:3402–3412PubMedCrossRef
41.
Zurück zum Zitat Mills J, Niewmierzycka A, Oloumi A, Rico B, St-Arnaud R, Mackenzie IR et al (2006) Critical role of integrin-linked kinase in granule cell precursor proliferation and cerebellar development. J Neurosci 26:830–840PubMedCrossRef Mills J, Niewmierzycka A, Oloumi A, Rico B, St-Arnaud R, Mackenzie IR et al (2006) Critical role of integrin-linked kinase in granule cell precursor proliferation and cerebellar development. J Neurosci 26:830–840PubMedCrossRef
42.
Zurück zum Zitat Rubin JB, Choi Y, Segal RA (2002) Cerebellar proteoglycans regulate sonic hedgehog responses during development. Development 129:2223–2232PubMed Rubin JB, Choi Y, Segal RA (2002) Cerebellar proteoglycans regulate sonic hedgehog responses during development. Development 129:2223–2232PubMed
43.
Zurück zum Zitat Pons S, Trejo JL, Martinez-Morales JR, Marti E (2001) Vitronectin regulates Sonic hedgehog activity during cerebellum development through CREB phosphorylation. Development 128:1481–1492PubMed Pons S, Trejo JL, Martinez-Morales JR, Marti E (2001) Vitronectin regulates Sonic hedgehog activity during cerebellum development through CREB phosphorylation. Development 128:1481–1492PubMed
44.
Zurück zum Zitat Vaillant C, Michos O, Orolicki S, Brellier F, Taieb S, Moreno E et al (2007) Protease nexin 1 and its receptor LRP modulate SHH signalling during cerebellar development. Development 134:1745–1754PubMedCrossRef Vaillant C, Michos O, Orolicki S, Brellier F, Taieb S, Moreno E et al (2007) Protease nexin 1 and its receptor LRP modulate SHH signalling during cerebellar development. Development 134:1745–1754PubMedCrossRef
45.
Zurück zum Zitat McCarthy RA, Argraves WS (2003) Megalin and the neurodevelopmental biology of sonic hedgehog and retinol. J Cell Sci 116:955–960PubMedCrossRef McCarthy RA, Argraves WS (2003) Megalin and the neurodevelopmental biology of sonic hedgehog and retinol. J Cell Sci 116:955–960PubMedCrossRef
46.
Zurück zum Zitat Willnow TE, Hilpert J, Armstrong SA, Rohlmann A, Hammer RE, Burns DK et al (1996) Defective forebrain development in mice lacking gp330/megalin. Proc Natl Acad Sci U S A 93:8460–8464PubMedCrossRef Willnow TE, Hilpert J, Armstrong SA, Rohlmann A, Hammer RE, Burns DK et al (1996) Defective forebrain development in mice lacking gp330/megalin. Proc Natl Acad Sci U S A 93:8460–8464PubMedCrossRef
47.
Zurück zum Zitat Li X, Herz J, Monard D (2006) Activation of ERK signaling upon alternative protease nexin-1 internalization mediated by syndecan-1. J Cell Biochem 99:936–951PubMedCrossRef Li X, Herz J, Monard D (2006) Activation of ERK signaling upon alternative protease nexin-1 internalization mediated by syndecan-1. J Cell Biochem 99:936–951PubMedCrossRef
48.
Zurück zum Zitat Nicot A, Lelievre V, Tam J, Waschek JA, DiCicco-Bloom E (2002) Pituitary adenylate cyclase-activating polypeptide and sonic hedgehog interact to control cerebellar granule precursor cell proliferation. J Neurosci 22:9244–9254PubMed Nicot A, Lelievre V, Tam J, Waschek JA, DiCicco-Bloom E (2002) Pituitary adenylate cyclase-activating polypeptide and sonic hedgehog interact to control cerebellar granule precursor cell proliferation. J Neurosci 22:9244–9254PubMed
49.
Zurück zum Zitat Fogarty MP, Emmenegger BA, Grasfeder LL, Oliver TG, Wechsler-Reya RJ (2007) Fibroblast growth factor blocks Sonic hedgehog signaling in neuronal precursors and tumor cells. Proc Natl Acad Sci U S A 104:2973–2978PubMedCrossRef Fogarty MP, Emmenegger BA, Grasfeder LL, Oliver TG, Wechsler-Reya RJ (2007) Fibroblast growth factor blocks Sonic hedgehog signaling in neuronal precursors and tumor cells. Proc Natl Acad Sci U S A 104:2973–2978PubMedCrossRef
50.
Zurück zum Zitat Lee A, Kessler JD, Read TA, Kaiser C, Corbeil D, Huttner WB et al (2005) Isolation of neural stem cells from the postnatal cerebellum. Nat Neurosci 8:723–729PubMedCrossRef Lee A, Kessler JD, Read TA, Kaiser C, Corbeil D, Huttner WB et al (2005) Isolation of neural stem cells from the postnatal cerebellum. Nat Neurosci 8:723–729PubMedCrossRef
51.
Zurück zum Zitat Rios I, Alvarez-Rodriguez R, Marti E, Pons S (2004) Bmp2 antagonizes sonic hedgehog-mediated proliferation of cerebellar granule neurones through Smad5 signalling. Development 131:3159–3168PubMedCrossRef Rios I, Alvarez-Rodriguez R, Marti E, Pons S (2004) Bmp2 antagonizes sonic hedgehog-mediated proliferation of cerebellar granule neurones through Smad5 signalling. Development 131:3159–3168PubMedCrossRef
52.
Zurück zum Zitat Alvarez-Rodriguez R, Barzi M, Berenguer J, Pons S (2007) Bone morphogenetic protein 2 opposes Shh-mediated proliferation in cerebellar granule cells through a TIEG-1-based regulation of Nmyc. J Biol Chem 282:37170–37180PubMedCrossRef Alvarez-Rodriguez R, Barzi M, Berenguer J, Pons S (2007) Bone morphogenetic protein 2 opposes Shh-mediated proliferation in cerebellar granule cells through a TIEG-1-based regulation of Nmyc. J Biol Chem 282:37170–37180PubMedCrossRef
53.
Zurück zum Zitat Gallo R, Zazzeroni F, Alesse E, Mincione C, Borello U, Buanne P et al (2002) REN: a novel, developmentally regulated gene that promotes neural cell differentiation. J Cell Biol 158:731–740PubMedCrossRef Gallo R, Zazzeroni F, Alesse E, Mincione C, Borello U, Buanne P et al (2002) REN: a novel, developmentally regulated gene that promotes neural cell differentiation. J Cell Biol 158:731–740PubMedCrossRef
54.
Zurück zum Zitat Argenti B, Gallo R, Di Marcotullio L, Ferretti E, Napolitano M, Canterini S et al (2005) Hedgehog antagonist REN(KCTD11) regulates proliferation and apoptosis of developing granule cell progenitors. J Neurosci 25:8338–8346PubMedCrossRef Argenti B, Gallo R, Di Marcotullio L, Ferretti E, Napolitano M, Canterini S et al (2005) Hedgehog antagonist REN(KCTD11) regulates proliferation and apoptosis of developing granule cell progenitors. J Neurosci 25:8338–8346PubMedCrossRef
55.
Zurück zum Zitat Klein AL, Zilian O, Suter U, Taylor V (2004) Murine numb regulates granule cell maturation in the cerebellum. Dev Biol 266:161–177PubMedCrossRef Klein AL, Zilian O, Suter U, Taylor V (2004) Murine numb regulates granule cell maturation in the cerebellum. Dev Biol 266:161–177PubMedCrossRef
56.
Zurück zum Zitat Di Marcotullio L, Ferretti E, Greco A, De Smaele E, Po A, Sico MA et al (2006) Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination. Nat Cell Biol 8:1415–1423PubMedCrossRef Di Marcotullio L, Ferretti E, Greco A, De Smaele E, Po A, Sico MA et al (2006) Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination. Nat Cell Biol 8:1415–1423PubMedCrossRef
57.
Zurück zum Zitat Wetmore C (2003) Sonic hedgehog in normal and neoplastic proliferation: insight gained from human tumors and animal models. Curr Opin Genet Dev 13:34–42PubMedCrossRef Wetmore C (2003) Sonic hedgehog in normal and neoplastic proliferation: insight gained from human tumors and animal models. Curr Opin Genet Dev 13:34–42PubMedCrossRef
58.
Zurück zum Zitat Fogarty MP, Kessler JD, Wechsler-Reya RJ (2005) Morphing into cancer: the role of developmental signaling pathways in brain tumor formation. J Neurobiol 64:458–475PubMedCrossRef Fogarty MP, Kessler JD, Wechsler-Reya RJ (2005) Morphing into cancer: the role of developmental signaling pathways in brain tumor formation. J Neurobiol 64:458–475PubMedCrossRef
59.
Zurück zum Zitat Eberhart CG (2007) In search of the medulloblast: neural stem cells and embryonal brain tumors. Neurosurg Clin N Am 18:59–69 viii–ixPubMedCrossRef Eberhart CG (2007) In search of the medulloblast: neural stem cells and embryonal brain tumors. Neurosurg Clin N Am 18:59–69 viii–ixPubMedCrossRef
60.
Zurück zum Zitat Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M et al (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci U S A 100:15178–15183PubMedCrossRef Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M et al (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci U S A 100:15178–15183PubMedCrossRef
61.
Zurück zum Zitat Schuller U, Heine VM, Mao J, Kho AT, Dillon AK, Han YG et al (2008) Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14:123–134PubMedCrossRef Schuller U, Heine VM, Mao J, Kho AT, Dillon AK, Han YG et al (2008) Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14:123–134PubMedCrossRef
62.
Zurück zum Zitat Yang ZJ, Ellis T, Markant SL, Read TA, Kessler JD, Bourboulas M et al (2008) Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell 14:135–145PubMedCrossRef Yang ZJ, Ellis T, Markant SL, Read TA, Kessler JD, Bourboulas M et al (2008) Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell 14:135–145PubMedCrossRef
63.
Zurück zum Zitat Gorlin RJ (1995) Nevoid basal cell carcinoma syndrome. Dermatol Clin 13:113–125PubMed Gorlin RJ (1995) Nevoid basal cell carcinoma syndrome. Dermatol Clin 13:113–125PubMed
64.
Zurück zum Zitat Pietsch T, Koch A, Wiestler OD (1997) Molecular genetic studies in medulloblastomas: evidence for tumor suppressor genes at the chromosomal regions 1q31-32 and 17p13. Klin Padiatr 209:150–155PubMedCrossRef Pietsch T, Koch A, Wiestler OD (1997) Molecular genetic studies in medulloblastomas: evidence for tumor suppressor genes at the chromosomal regions 1q31-32 and 17p13. Klin Padiatr 209:150–155PubMedCrossRef
65.
Zurück zum Zitat Taylor MD, Liu L, Raffel C, Hui CC, Mainprize TG, Zhang X et al (2002) Mutations in SUFU predispose to medulloblastoma. Nat Genet 31:306–310PubMedCrossRef Taylor MD, Liu L, Raffel C, Hui CC, Mainprize TG, Zhang X et al (2002) Mutations in SUFU predispose to medulloblastoma. Nat Genet 31:306–310PubMedCrossRef
66.
Zurück zum Zitat Reifenberger J, Wolter M, Weber RG, Megahed M, Ruzicka T, Lichter P et al (1998) Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res 58:1798–1803PubMed Reifenberger J, Wolter M, Weber RG, Megahed M, Ruzicka T, Lichter P et al (1998) Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res 58:1798–1803PubMed
67.
Zurück zum Zitat Weiner HL, Bakst R, Hurlbert MS, Ruggiero J, Ahn E, Lee WS et al (2002) Induction of medulloblastomas in mice by sonic hedgehog, independent of Gli1. Cancer Res 62:6385–6389PubMed Weiner HL, Bakst R, Hurlbert MS, Ruggiero J, Ahn E, Lee WS et al (2002) Induction of medulloblastomas in mice by sonic hedgehog, independent of Gli1. Cancer Res 62:6385–6389PubMed
68.
Zurück zum Zitat Rao G, Pedone CA, Coffin CM, Holland EC, Fults DW (2003) c-Myc enhances sonic hedgehog-induced medulloblastoma formation from nestin-expressing neural progenitors in mice. Neoplasia 5:198–204PubMed Rao G, Pedone CA, Coffin CM, Holland EC, Fults DW (2003) c-Myc enhances sonic hedgehog-induced medulloblastoma formation from nestin-expressing neural progenitors in mice. Neoplasia 5:198–204PubMed
69.
Zurück zum Zitat Goodrich LV, Milenkovic L, Higgins KM, Scott MP (1997) Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277:1109–1113PubMedCrossRef Goodrich LV, Milenkovic L, Higgins KM, Scott MP (1997) Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277:1109–1113PubMedCrossRef
70.
Zurück zum Zitat Hallahan AR, Pritchard JI, Hansen S, Benson M, Stoeck J, Hatton BA et al (2004) The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Res 64:7794–7800PubMedCrossRef Hallahan AR, Pritchard JI, Hansen S, Benson M, Stoeck J, Hatton BA et al (2004) The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Res 64:7794–7800PubMedCrossRef
71.
Zurück zum Zitat Mao J, Ligon KL, Rakhlin EY, Thayer SP, Bronson RT, Rowitch D et al (2006) A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway. Cancer Res 66:10171–10178PubMedCrossRef Mao J, Ligon KL, Rakhlin EY, Thayer SP, Bronson RT, Rowitch D et al (2006) A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway. Cancer Res 66:10171–10178PubMedCrossRef
72.
Zurück zum Zitat Kimura H, Stephen D, Joyner A, Curran T (2005) Gli1 is important for medulloblastoma formation in Ptc1+/− mice. Oncogene 24:4026–4036PubMed Kimura H, Stephen D, Joyner A, Curran T (2005) Gli1 is important for medulloblastoma formation in Ptc1+/− mice. Oncogene 24:4026–4036PubMed
73.
Zurück zum Zitat Wetmore C, Eberhart DE, Curran T (2001) Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched. Cancer Res 61:513–516PubMed Wetmore C, Eberhart DE, Curran T (2001) Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched. Cancer Res 61:513–516PubMed
74.
Zurück zum Zitat Lee Y, Kawagoe R, Sasai K, Li Y, Russell HR, Curran T et al (2007) Loss of suppressor-of-fused function promotes tumorigenesis. Oncogene 26:6442–6447PubMedCrossRef Lee Y, Kawagoe R, Sasai K, Li Y, Russell HR, Curran T et al (2007) Loss of suppressor-of-fused function promotes tumorigenesis. Oncogene 26:6442–6447PubMedCrossRef
75.
Zurück zum Zitat Lee Y, Miller HL, Jensen P, Hernan R, Connelly M, Wetmore C et al (2003) A molecular fingerprint for medulloblastoma. Cancer Res 63:5428–5437PubMed Lee Y, Miller HL, Jensen P, Hernan R, Connelly M, Wetmore C et al (2003) A molecular fingerprint for medulloblastoma. Cancer Res 63:5428–5437PubMed
76.
Zurück zum Zitat Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME et al (2002) Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415:436–442PubMedCrossRef Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME et al (2002) Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415:436–442PubMedCrossRef
77.
Zurück zum Zitat Hahn H, Wojnowski L, Specht K, Kappler R, Calzada-Wack J, Potter D et al (2000) Patched target Igf2 is indispensable for the formation of medulloblastoma and rhabdomyosarcoma. J Biol Chem 275:28341–28344PubMedCrossRef Hahn H, Wojnowski L, Specht K, Kappler R, Calzada-Wack J, Potter D et al (2000) Patched target Igf2 is indispensable for the formation of medulloblastoma and rhabdomyosarcoma. J Biol Chem 275:28341–28344PubMedCrossRef
78.
Zurück zum Zitat Rao G, Pedone CA, Del Valle L, Reiss K, Holland EC, Fults DW (2004) Sonic hedgehog and insulin-like growth factor signaling synergize to induce medulloblastoma formation from nestin-expressing neural progenitors in mice. Oncogene 23:6156–6162PubMedCrossRef Rao G, Pedone CA, Del Valle L, Reiss K, Holland EC, Fults DW (2004) Sonic hedgehog and insulin-like growth factor signaling synergize to induce medulloblastoma formation from nestin-expressing neural progenitors in mice. Oncogene 23:6156–6162PubMedCrossRef
79.
Zurück zum Zitat Kenney AM, Widlund HR, Rowitch DH (2004) Hedgehog and PI-3 kinase signaling converge on Nmyc1 to promote cell cycle progression in cerebellar neuronal precursors. Development 131:217–228PubMedCrossRef Kenney AM, Widlund HR, Rowitch DH (2004) Hedgehog and PI-3 kinase signaling converge on Nmyc1 to promote cell cycle progression in cerebellar neuronal precursors. Development 131:217–228PubMedCrossRef
80.
Zurück zum Zitat Browd SR, Kenney AM, Gottfried ON, Yoon JW, Walterhouse D, Pedone CA et al (2006) N-myc can substitute for insulin-like growth factor signaling in a mouse model of sonic hedgehog-induced medulloblastoma. Cancer Res 66:2666–2672PubMedCrossRef Browd SR, Kenney AM, Gottfried ON, Yoon JW, Walterhouse D, Pedone CA et al (2006) N-myc can substitute for insulin-like growth factor signaling in a mouse model of sonic hedgehog-induced medulloblastoma. Cancer Res 66:2666–2672PubMedCrossRef
81.
Zurück zum Zitat Ferretti E, De Smaele E, Miele E, Laneve P, Po A, Pelloni M et al (2008) Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells. EMBO J 27:2616–2627PubMedCrossRef Ferretti E, De Smaele E, Miele E, Laneve P, Po A, Pelloni M et al (2008) Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells. EMBO J 27:2616–2627PubMedCrossRef
82.
Zurück zum Zitat Di Marcotullio L, Ferretti E, De Smaele E, Argenti B, Mincione C, Zazzeroni F et al (2004) REN(KCTD11) is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma. Proc Natl Acad Sci U S A 101:10833–10838PubMedCrossRef Di Marcotullio L, Ferretti E, De Smaele E, Argenti B, Mincione C, Zazzeroni F et al (2004) REN(KCTD11) is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma. Proc Natl Acad Sci U S A 101:10833–10838PubMedCrossRef
83.
Zurück zum Zitat Ferretti E, De Smaele E, Di Marcotullio L, Screpanti I, Gulino A (2005) Hedgehog checkpoints in medulloblastoma: the chromosome 17p deletion paradigm. Trends Mol Med 11:537–545PubMedCrossRef Ferretti E, De Smaele E, Di Marcotullio L, Screpanti I, Gulino A (2005) Hedgehog checkpoints in medulloblastoma: the chromosome 17p deletion paradigm. Trends Mol Med 11:537–545PubMedCrossRef
84.
Zurück zum Zitat Briggs KJ, Corcoran-Schwartz IM, Zhang W, Harcke T, Devereux WL, Baylin SB et al (2008) Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma. Genes Dev 22:770–785PubMedCrossRef Briggs KJ, Corcoran-Schwartz IM, Zhang W, Harcke T, Devereux WL, Baylin SB et al (2008) Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma. Genes Dev 22:770–785PubMedCrossRef
85.
Zurück zum Zitat Berman DM, Karhadkar SS, Hallahan AR, Pritchard JI, Eberhart CG, Watkins DN et al (2002) Medulloblastoma growth inhibition by hedgehog pathway blockade. Science 297:1559–1561PubMedCrossRef Berman DM, Karhadkar SS, Hallahan AR, Pritchard JI, Eberhart CG, Watkins DN et al (2002) Medulloblastoma growth inhibition by hedgehog pathway blockade. Science 297:1559–1561PubMedCrossRef
86.
Zurück zum Zitat Romer JT, Kimura H, Magdaleno S, Sasai K, Fuller C, Baines H et al (2004) Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+/−)p53(−/−) mice. Cancer Cell 6:229–240PubMedCrossRef Romer JT, Kimura H, Magdaleno S, Sasai K, Fuller C, Baines H et al (2004) Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+/−)p53(−/−) mice. Cancer Cell 6:229–240PubMedCrossRef
87.
Zurück zum Zitat Rubin JB, Kung AL, Klein RS, Chan JA, Sun Y, Schmidt K et al (2003) A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc Natl Acad Sci U S A 100:13513–13518PubMedCrossRef Rubin JB, Kung AL, Klein RS, Chan JA, Sun Y, Schmidt K et al (2003) A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc Natl Acad Sci U S A 100:13513–13518PubMedCrossRef
88.
Zurück zum Zitat Corcoran RB, Bachar Raveh T, Barakat MT, Lee EY, Scott MP (2008) Insulin-like growth factor 2 is required for progression to advanced medulloblastoma in patched1 heterozygous mice. Cancer Res 68:8788–8795PubMedCrossRef Corcoran RB, Bachar Raveh T, Barakat MT, Lee EY, Scott MP (2008) Insulin-like growth factor 2 is required for progression to advanced medulloblastoma in patched1 heterozygous mice. Cancer Res 68:8788–8795PubMedCrossRef
89.
Zurück zum Zitat Corcoran RB, Scott MP (2006) Oxysterols stimulate Sonic hedgehog signal transduction and proliferation of medulloblastoma cells. Proc Natl Acad Sci U S A 103:8408–8413PubMedCrossRef Corcoran RB, Scott MP (2006) Oxysterols stimulate Sonic hedgehog signal transduction and proliferation of medulloblastoma cells. Proc Natl Acad Sci U S A 103:8408–8413PubMedCrossRef
90.
Zurück zum Zitat Grimmer MR, Weiss WA (2008) BMPs oppose Math1 in cerebellar development and in medulloblastoma. Genes Dev 22:693–699PubMedCrossRef Grimmer MR, Weiss WA (2008) BMPs oppose Math1 in cerebellar development and in medulloblastoma. Genes Dev 22:693–699PubMedCrossRef
91.
Zurück zum Zitat Duplan SM, Theoret Y, Kenigsberg RL (2002) Antitumor activity of fibroblast growth factors (FGFs) for medulloblastoma may correlate with FGF receptor expression and tumor variant. Clin Cancer Res 8:246–257PubMed Duplan SM, Theoret Y, Kenigsberg RL (2002) Antitumor activity of fibroblast growth factors (FGFs) for medulloblastoma may correlate with FGF receptor expression and tumor variant. Clin Cancer Res 8:246–257PubMed
92.
Zurück zum Zitat Vachon P, Girard C, Theoret Y (2004) Effects of basic fibroblastic growth factor on the growth of human medulloblastoma xenografts. J Neurooncol 67:139–146PubMedCrossRef Vachon P, Girard C, Theoret Y (2004) Effects of basic fibroblastic growth factor on the growth of human medulloblastoma xenografts. J Neurooncol 67:139–146PubMedCrossRef
93.
Zurück zum Zitat Rohatgi R, Milenkovic L, Scott MP (2007) Patched1 regulates hedgehog signaling at the primary cilium. Science 317:372–376PubMedCrossRef Rohatgi R, Milenkovic L, Scott MP (2007) Patched1 regulates hedgehog signaling at the primary cilium. Science 317:372–376PubMedCrossRef
94.
Zurück zum Zitat Chizhikov VV, Davenport J, Zhang Q, Shih EK, Cabello OA, Fuchs JL et al (2007) Cilia proteins control cerebellar morphogenesis by promoting expansion of the granule progenitor pool. J Neurosci 27:9780–9789PubMedCrossRef Chizhikov VV, Davenport J, Zhang Q, Shih EK, Cabello OA, Fuchs JL et al (2007) Cilia proteins control cerebellar morphogenesis by promoting expansion of the granule progenitor pool. J Neurosci 27:9780–9789PubMedCrossRef
95.
Zurück zum Zitat Spassky N, Han YG, Aguilar A, Strehl L, Besse L, Laclef C et al (2008) Primary cilia are required for cerebellar development and Shh-dependent expansion of progenitor pool. Dev Biol 317:246–259PubMedCrossRef Spassky N, Han YG, Aguilar A, Strehl L, Besse L, Laclef C et al (2008) Primary cilia are required for cerebellar development and Shh-dependent expansion of progenitor pool. Dev Biol 317:246–259PubMedCrossRef
96.
Zurück zum Zitat Millen KJ, Gleeson JG (2008) Cerebellar development and disease. Curr Opin Neurobiol 18:12–19PubMedCrossRef Millen KJ, Gleeson JG (2008) Cerebellar development and disease. Curr Opin Neurobiol 18:12–19PubMedCrossRef
97.
Zurück zum Zitat Louie CM, Gleeson JG (2005) Genetic basis of Joubert syndrome and related disorders of cerebellar development. Hum Mol Genet 14(Spec No. 2):R235–R242PubMedCrossRef Louie CM, Gleeson JG (2005) Genetic basis of Joubert syndrome and related disorders of cerebellar development. Hum Mol Genet 14(Spec No. 2):R235–R242PubMedCrossRef
98.
99.
Zurück zum Zitat Latash ML, Corcos DM (1991) Kinematic and electromyographic characteristics of single-joint movements of individuals with Down syndrome. Am J Ment Retard 96:189–201PubMed Latash ML, Corcos DM (1991) Kinematic and electromyographic characteristics of single-joint movements of individuals with Down syndrome. Am J Ment Retard 96:189–201PubMed
100.
Zurück zum Zitat Moldrich RX, Dauphinot L, Laffaire J, Rossier J, Potier MC (2007) Down syndrome gene dosage imbalance on cerebellum development. Prog Neurobiol 82:87–94PubMedCrossRef Moldrich RX, Dauphinot L, Laffaire J, Rossier J, Potier MC (2007) Down syndrome gene dosage imbalance on cerebellum development. Prog Neurobiol 82:87–94PubMedCrossRef
101.
Zurück zum Zitat Roper RJ, Baxter LL, Saran NG, Klinedinst DK, Beachy PA, Reeves RH (2006) Defective cerebellar response to mitogenic Hedgehog signaling in Down [corrected] syndrome mice. Proc Natl Acad Sci U S A 103:1452–1456PubMedCrossRef Roper RJ, Baxter LL, Saran NG, Klinedinst DK, Beachy PA, Reeves RH (2006) Defective cerebellar response to mitogenic Hedgehog signaling in Down [corrected] syndrome mice. Proc Natl Acad Sci U S A 103:1452–1456PubMedCrossRef
102.
Zurück zum Zitat Dakubo GD, Beug ST, Mazerolle CJ, Thurig S, Wang Y, Wallace VA (2008) Control of glial precursor cell development in the mouse optic nerve by sonic hedgehog from retinal ganglion cells. Brain Res 1228:27–42PubMedCrossRef Dakubo GD, Beug ST, Mazerolle CJ, Thurig S, Wang Y, Wallace VA (2008) Control of glial precursor cell development in the mouse optic nerve by sonic hedgehog from retinal ganglion cells. Brain Res 1228:27–42PubMedCrossRef
103.
Zurück zum Zitat Charron F, Stein E, Jeong J, McMahon AP, Tessier-Lavigne M (2003) The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell 113:11–23PubMedCrossRef Charron F, Stein E, Jeong J, McMahon AP, Tessier-Lavigne M (2003) The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell 113:11–23PubMedCrossRef
104.
Zurück zum Zitat So PL, Yip PK, Bunting S, Wong LF, Mazarakis ND, Hall S et al (2006) Interactions between retinoic acid, nerve growth factor and sonic hedgehog signalling pathways in neurite outgrowth. Dev Biol 298:167–175PubMedCrossRef So PL, Yip PK, Bunting S, Wong LF, Mazarakis ND, Hall S et al (2006) Interactions between retinoic acid, nerve growth factor and sonic hedgehog signalling pathways in neurite outgrowth. Dev Biol 298:167–175PubMedCrossRef
Metadaten
Titel
SHH Pathway and Cerebellar Development
verfasst von
Catherine Vaillant
Denis Monard
Publikationsdatum
01.09.2009
Verlag
Springer-Verlag
Erschienen in
The Cerebellum / Ausgabe 3/2009
Print ISSN: 1473-4222
Elektronische ISSN: 1473-4230
DOI
https://doi.org/10.1007/s12311-009-0094-8

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