Hedgehog–GLI signaling and the growth of the brain (original) (raw)

• Qian, X., Davis, A. A., Goderie, S. K. & Temple, S. FGF2 concentration regulates the generation of neurons and glia from multipotent cortical stem cells. Neuron 18, 81–93 (1997).
  Article CAS PubMed Google Scholar
• Qian, X., Goderie, S. K., Shen, Q., Stern, J. H. & Temple, S. Intrinsic programs of patterned cell lineages in isolated vertebrate CNS ventricular zone cells. Development 125, 3143–3152 (1998).
  Article CAS PubMed Google Scholar
• Raballo, R. et al. Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex. J. Neurosci. 20, 5012–5023 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Lillien, L. & Raphael, H. BMP and FGF regulate the development of EGF-responsive neural progenitor cells. Development 127, 4993–5005 (2000).
  Article CAS PubMed Google Scholar
• Tropepe, V. et al. Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon. Dev. Biol. 208, 166–188 (1999).
  Article CAS PubMed Google Scholar
• Cheng, Y., Tao, Y., Black, I. B. & DiCicco-Bloom, E. A single peripheral injection of basic fibroblast growth factor (bFGF) stimulates granule cell production and increases cerebellar growth in newborn rats. J. Neurobiol. 46, 220–229 (2001).Shows the effects of FGF on cerebellar growth.
  Article CAS PubMed Google Scholar
• Vaccarino, F. M. et al. Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis. Nature Neurosci. 2, 246–253 (1999).Shows that FGF signalling has an important role in the growth of the cortex.
  Article CAS PubMed Google Scholar
• Rakic, P. A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution. Trends Neurosci. 18, 383–388 (1995).
  Article CAS PubMed Google Scholar
• Rakic, P. Radial unit hypothesis of neocortical expansion. Novartis Found. Symp. 228, 30–42 (2000).
  CAS PubMed Google Scholar
• Dahmane, N. et al. The Shh–Gli pathway modulates the normal and abnormal growth of the dorsal brain. Development 128 (in the press).Provides evidence for a role of SHH signalling in controlling the growth of the dorsal brain, and the initiation and possible maintenance of brain tumorigenesis, including gliomagenesis.
• Ruiz i Altaba, A. Gli proteins encode context-dependent positive and negative functions: implications for development and disease. Development 126, 3205–3216 (1999).Indicates activator and repressor functions of vertebrate Glis.
  Article PubMed 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
• Riddle, R. D., Johnson, R. L., Laufer, E. & Tabin, C. J. Sonic hedgehog mediates the polarizing activity of the ZPA. Cell 75, 1401–1416 (1993).Reports the first insights into HH signalling in vertebrates (see also references 14–16).
  Article CAS PubMed Google Scholar
• Krauss, S., Concordet, J. P. & Ingham, P. W. A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos. Cell 75, 1431–1444 (1993).
  Article CAS PubMed Google Scholar
• Echelard, Y. et al. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell 75, 1417–1430 (1993).
  Article CAS PubMed Google Scholar
• Roelink, H. et al. Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of Hedgehog expressed by the notochord. Cell 76, 761–775 (1994).
  Article CAS PubMed Google Scholar
• Porter, J. A., Young, K. E. & Beachy, P. A. Cholesterol modification of Hedgehog signaling proteins in animal development. Science 274, 255–259 (1996).
  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
• Lee, J., Platt, K. A., Censullo, P. & Ruiz i Altaba, A. Gli1 is a target of Sonic hedgehog that induces ventral neural tube development. Development 124, 2537–2552 (1997).
  Article CAS PubMed Google Scholar
• Hynes, M. et al. Control of cell pattern in the neural tube by the zinc finger transcription factor and oncogene Gli-1. Neuron 19, 15–26 (1997).
  Article CAS PubMed Google Scholar
• Ruiz i Altaba, A. Catching a Gli-mpse of Hedgehog. Cell 90, 193–196 (1997).
  Article 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).Elaborates on the regulation of Gli transcription by SHH signalling, showing an antagonism between SHH/Gli1 and Gli3, as well as providing evidence for the combinatorial and context-dependent action of the Gli proteins.
  Article PubMed Google Scholar
• Mo, R. et al. Specific and redundant functions of Gli2 and Gli3 zinc finger genes in skeletal patterning and development. Development 124, 113–123 (1997).Genetic evidence that Gli2 and Gli3 have partially overlapping functions in mice.
  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).Shows that vertebrate Gli proteins have specific functions in vivo ; also shows the differential regulation of repressor and activator functions by HH signalling in flies.
  Article PubMed Google Scholar
• Litingtung, Y. & Chiang, C. Specification of ventral neuron types is mediated by an antagonistic interaction between Shh and Gli3. Nature Neurosci. 3, 979–985 (2000).Reports the rescue of aspects of ventral differentiation in double SHH/Gli3 mutants, indicating that SHH acts at least in part by repressing Gli3 function.
  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).A superb and accessible review on a decade of ground-breaking work on cell specification in the spinal cord.
  Article CAS PubMed Google Scholar
• Hynes, M. et al. Induction of midbrain dopaminergic neurons by Sonic hedgehog. Neuron 15, 35–44 (1995).
  Article CAS PubMed Google Scholar
• Chiang, C. et al. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383, 407–413 (1996).A genetic demonstration that SHH is required for normal ventral CNS development, as well as for the development of many other organs and tissues.
  Article CAS PubMed Google Scholar
• Ericson, J., Muhr, J., Jessell, T. M. & Edlund, T. Sonic hedgehog: a common signal for ventral patterning along the rostrocaudal axis of the neural tube. Int. J. Dev. Biol. 39, 809–816 (1995).
  CAS 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
• Kohtz, J. D., Baker, D. P., Corte, G. & Fishell, G. Regionalization within the mammalian telencephalon is mediated by changes in responsiveness to Sonic Hedgehog. Development 125, 5079–5089 (1998).
  Article CAS PubMed Google Scholar
• Ye, W., Shimamura, K., Rubenstein, J. L., Hynes, M. A. & Rosenthal, A. FGF and Shh signals control dopaminergic and serotonergic cell fate in the anterior neural plate. Cell 93, 755–766 (1998).
  Article CAS PubMed Google Scholar
• Agarwala, S., Sanders, T. A. & Ragsdale, C. W. Sonic Hedgehog control of size and shape in midbrain pattern formation. Science 291, 2147–2150 (2001).Shows that early ectopic SHH can ventralize and repattern the dorsal midbrain.
  Article CAS PubMed Google Scholar
• Poncet, C. et al. Induction of oligodendrocyte progenitors in the trunk neural tube by ventralizing signals: effects of notochord and floor plate grafts, and of sonic hedgehog. Mech. Dev. 60, 13–32 (1996).
  Article CAS PubMed Google Scholar
• Pringle, N. P. et al. Determination of neuroepithelial cell fate: induction of the oligodendrocyte lineage by ventral midline cells and sonic hedgehog. Dev. Biol. 177, 30–42 (1996).
  Article CAS PubMed Google Scholar
• Orentas, D. M., Hayes, J. E., Dyer, K. L. & Miller, R. H. Sonic hedgehog signaling is required during the appearance of spinal cord oligodendrocyte precursors. Development 126, 2419–2429 (1999).
  Article CAS PubMed Google Scholar
• Lu, Q. R. et al. Sonic hedgehog-regulated oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system. Neuron 25, 317–329 (2000).
  Article CAS PubMed Google Scholar
• Soula, C. et al. Distinct sites of origin of oligodendrocytes and somatic motoneurons in the chick spinal cord: oligodendrocytes arise from Nkx2.2-expressing progenitors by a Shh-dependent mechanism. Development 128, 1369–1379 (2001).
  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).Shows the requirement of SHH signalling in the development and growth of the cerebellum, providing the basis for a model of morphological plasticity of this structure. Also provides a rational cellular context for the development of medulloblastomas (see also references 40 and 41).
  Article 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).
  Article CAS 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
• Traiffort, E., Charytoniuk, D. A., Faure, H. & Ruat, M. Regional distribution of sonic sedgehog, patched, and smoothened mRNA in the adult rat brain. J. Neurochem. 70, 1327–1330 (1998).This work indicates the presence of SHH signalling in the mature brain.
  Article CAS PubMed Google Scholar
• Traiffort E. et al. Discrete localizations of hedgehog signalling components in the developing and adult rat nervous system. Eur. J. Neurosci. 11, 3199–3214 (1999).
  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).Reports the early role of SHH as a mitogen in the embryonic spinal cord.
  Article CAS PubMed PubMed Central 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).Shows the ability of Gli1 to induce tumours in vivo , and the expression of GLI1 in virtually all sporadic human basal cell carcinomas (BCCs), the most common human cancer. This work led to the proposal that all sporadic human BCCs derive from activation of the SHH–GLI pathway, providing a basis for this tumour type and a potential rational therapy.
  Article CAS PubMed Google Scholar
• Bayer, S. A. & Altman, J. Neocortical Development (Raven Press, New York, 1991).
  Google Scholar
• Clark, D. A., Mitra, P. P. & Wang, S. S. Scalable architecture in mammalian brains. Nature 411, 189–193 (2001).
  Article CAS PubMed Google Scholar
• Kornack, D. R. Neurogenesis and the evolution of cortical diversity: mode, tempo, and partitioning during development and persistence in adulthood. Brain Behav. Evol. 55, 336–344 (2000).
  Article CAS PubMed Google Scholar
• Temple, S. Stem cell plasticity — building the brain of our dreams. Nature Rev. Neurosci. 2, 513–520 (2001).
  Article CAS 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
• Caviness, V. S. Jr & Takahashi, T. Proliferative events in the cerebral ventricular zone. Brain Dev. 17, 159–163 (1995).
  Article PubMed Google Scholar
• Altman, J. & Bayer, S. A. Development of the Cerebellar System. In Relation to its Evolution, Structure, and Functions (CRC Press, New York, 1997).
  Google Scholar
• Hatten, M. E. & Heintz, N. Mechanisms of neural patterning and specification in the developing cerebellum. Annu. Rev. Neurosci. 18, 385–408 (1995).
  Article CAS PubMed Google Scholar
• Wang, V. Y. & Zoghbi, H. Y. Genetic regulation of cerebellar development. Nature Rev. Neurosci. 2, 484–491 (2001).
  Article CAS Google Scholar
• Alder, J., Lee, K. J., Jessell, T. M. & Hatten, M. E. Generation of cerebellar granule neurons in vivo by transplantation of BMP-treated neural progenitor cells. Nature Neurosci. 2, 535–540 (1999).Shows that the early specification and generation of granule neuron precursors in the rhombic lip is by a BMP-dependent, SHH-independent mechanism.
  Article CAS PubMed Google Scholar
• Sato, T., Araki, I. & Nakamura, H. Inductive signal and tissue responsiveness defining the tectum and the cerebellum. Development 128, 2461–2469 (2001).
  Article CAS PubMed Google Scholar
• Xu, J., Liu, Z. & Ornitz, D. M. Temporal and spatial gradients of Fgf8 and Fgf17 regulate proliferation and differentiation of midline cerebellar structures. Development 127, 1833–1843 (2000).
  Article CAS PubMed 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).Shows the requirement of SHH signalling at different times in the cell cycle.
  Article CAS PubMed Google Scholar
• Ben-Arie, N. et al. Math1 is essential for genesis of cerebellar granule neurons. Nature 390, 169–172 (1997).
  Article CAS PubMed Google Scholar
• Watanabe, Y. & Nakamura, H. Control of chick tectum territory along dorsoventral axis by Sonic hedgehog. Development 127, 1131–1140 (2000).
  Article CAS PubMed Google Scholar
• Hatten, M. E. Central nervous system neuronal migration. Annu. Rev. Neurosci. 22, 511–539 (1999).
  Article CAS PubMed Google Scholar
• Pons, S., Trejo, J. L., Martinez-Morales, J. R. & Marti, E. Vitronectin regulates Sonic hedgehog activity during cerebellum development through CREB phosphorylation. Development 128, 1481–1492 (2001).
  Article CAS PubMed Google Scholar
• Herrup, K. Thoughts on the cerebellum as a model for cerebral cortical development and evolution. Novartis Found. Symp. 228, 15–24 (2000).
  CAS PubMed Google Scholar
• Xuan, S. et al. Winged helix transcription factor BF-1 is essential for the development of the cerebral hemispheres. Neuron 14, 1141–1152 (1995).
  Article CAS PubMed Google Scholar
• Theil, T., Alvarez-Bolado, G., Walter, A. & Ruther, U. Gli3 is required for Emx gene expression during dorsal telencephalon development. Development 126, 3561–3571 (1999).
  Article CAS PubMed Google Scholar
• Toole, S. Ragsdale, C. W. & Grove, E. A. Dorsoventral patterning of the mouse telencephalon is disrupted in the mouse mutant extra-toes. Dev. Biol. 217, 254–265 (2000).
  Article CAS Google Scholar
• Kornack, D. R. & Rakic, P. Changes in cell-cycle kinetics during the development and evolution of primate neocortex. Proc. Natl Acad. Sci. USA 95, 1242–1246 (1998).
  Article CAS PubMed PubMed Central 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 interruptus protein to the nucleus and converts it to a repressor. Cell 89, 1043–1053 (1997).Demonstration of repressor activity by proteolytic cleavage of the Drosophila Gli.
  Article CAS PubMed Google Scholar
• Methot, N. & Basler, K. Hedgehog controls limb development by regulating the activities of distinct transcriptional activator and repressor forms of Cubitus interruptus. Cell 96, 819–831 (1999).A detailed analysis of the control of activator and repressor functions of Ci, the Drosophila Gli homologue.
  Article CAS PubMed Google Scholar
• Shin, S. H., Kogerman, P., Lindstrom, E., Toftgard, R. & Biesecker, L. G. GLI3 mutations in human disorders mimic Drosophila Cubitus interruptus protein functions and localization. Proc. Natl Acad. Sci. USA 96, 2880–2884 (1999).Structure–function analysis of Gli3 and its repressor activity.
  Article CAS PubMed PubMed Central Google Scholar
• Dai, P. et al. Sonic Hedgehog-induced activation of the Gli1 promoter is mediated by GLI3. J. Biol. Chem. 274, 8143–8152 (1999).
  Article CAS PubMed Google Scholar
• Wang, B., Fallon, J. F. & Beachy, P. A. Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb. Cell 100, 423–434 (2000).Shows the presence of smaller-than-full-length Gli3 bands in chick limb bud western blots, indicating the existence of putative repressor forms in vivo.
  Article 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).Shows that mouse mutants for Gli1 are viable.
  Article CAS PubMed Google Scholar
• Matise, M. P., Epstein, D. J., Park, H. L., Platt, K. A. & Joyner, A. L. Gli2 is required for induction of floor plate and adjacent cells, but not most ventral neurons in the mouse central nervous system. Development 125, 2759–2770 (1998).
  Article CAS PubMed Google Scholar
• Smith, M. J. et al. GLI-2 modulates retroviral gene expression. J. Virol. 75, 2301–2313 (2001).
  Article CAS PubMed PubMed Central 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
• Gallet, A., Angelats, C., Kerridge, S. & Therond, P. P. Cubitus interruptus-independent transduction of the Hedgehog signal in Drosophila. Development 127, 5509–5522 (2000).
  Article CAS PubMed Google Scholar
• Sasaki, H., Nishizaki, Y., Hui, C., Nakafuku, M. & Kondoh, H. Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling. Development 126, 3915–3924 (1999).Evidence that the early mediation of SHH signals involves Gli2 function.
  Article CAS PubMed Google Scholar
• Hui, C. C & Joyner, A. L. A mouse model of Greig cephalopolysyndactyly syndrome: the extra-toes mutation contains an intragenic deletion of the Gli3 gene. Nature Genet. 3, 241–246 (1993).
  Article CAS PubMed Google Scholar
• Franz, T. Extra-toes (Xt) homozygous mice demonstrate a role for the Gli3 gene in the development of the forebrain. Acta Anat. 150, 38–44 (1994). | PubMed |
  Article CAS 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
• 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).An exploration of the ways in which SHH affects the cell cycle, providing evidence that it acts on G1 cyclins.
  Article CAS PubMed PubMed Central Google Scholar
• Huard, J. M., Forster, C. C., Carter, M. L., Sicinski, P. & Ross, M. E. Cerebellar histogenesis is disturbed in mice lacking cyclin D2. Development 126, 1927–1935 (1999).
  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
• Miyazawa, K., Himi, T., Garcia, V., Yamagishi, H., Sato, S. & Ishizaki, Y. A role for p27/Kip1 in the control of cerebellar granule cell precursor proliferation. J. Neurosci. 20, 5756–5763 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Sherr, C. J. & Roberts, J. M. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 13, 1501–1512 (1999).
  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).
  Article CAS Google Scholar
• Pepinsky, R. B. et al. Identification of a palmitic acid-modified form of human Sonic hedgehog. J. Biol. Chem. 273, 14037–14045 (1998).
  Article CAS PubMed Google Scholar
• Zeng, X. et al. A freely diffusible form of Sonic hedgehog mediates long-range signalling. Nature 411, 716–720 (2001).
  Article CAS PubMed Google Scholar
• Gritli-Linde, A., Lewis, P., McMahon, A. P. & Linde, A. The whereabouts of a morphogen: direct evidence for short- and graded long-range activity of hedgehog signaling peptides. Dev. Biol. 236, 364–386 (2001).Fantastic visualization of SHH protein far from its sources.
  Article CAS PubMed Google Scholar
• Heemskerk, J. & DiNardo, S. Drosophila Hedgehog acts as a morphogen in cellular patterning. Cell 76, 449–460 (1994).
  Article CAS PubMed Google Scholar
• Chen, Y. & Struhl, G. Dual roles for Patched in sequestering and transducing Hedgehog. Cell 87, 553–563 (1996).
  Article CAS PubMed Google Scholar
• Mullor, J. L., Calleja, M., Capdevila, J. & Guerrero, I. Hedgehog activity, independent of Decapentaplegic, participates in wing disc patterning. Development 124, 1227–1237 (1997).This work, together with references 97 and 98 , provides evidence that HH acts as a morphogen.
  Article CAS PubMed Google Scholar
• Mullor, J. L. & Guerrero, I. A gain-of-function mutant of patched dissects different responses to Hedgehog gradient. Dev. Biol. 228, 211–224 (2000).
  Article CAS PubMed Google Scholar
• Strigini, M. & Cohen, S. M. A Hedgehog activity gradient contributes to AP axial patterning of the Drosophila wing. Development 124, 4697–4705 (1997).
  Article CAS PubMed Google Scholar
• Briscoe, J., Chen, Y., Jessell, T. M. & Struhl, G. A hedgehog-insensitive form of patched provides evidence for direct long-range morphogen activity of sonic hedgehog in the neural tube. Mol. Cell 7, 1279–1291 (2001).
  Article CAS PubMed Google Scholar
• Hynes, M. et al. The seven-transmembrane receptor Smoothened cell-autonomously induces multiple ventral cell types. Nature Neurosci. 3, 41–46 (2000).
  Article CAS PubMed Google Scholar
• Lewis, P. M. et al. Modification of Sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1. Cell 105, 599–612 (2001).
  Article CAS PubMed Google Scholar
• Bellaiche, Y., The, I. & Perrimon, N. Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion. Nature 394, 85–88 (1998).
  Article CAS PubMed Google Scholar
• Burke, R. et al. Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified Hedgehog from signaling cells. Cell 99, 803–815 (1999).
  Article CAS PubMed Google Scholar
• Martin, V., Carrillo, G., Torroja, C. & Guerrero, I. The sterol-sensing domain of Patched protein seems to control Smoothened activity through Patched vesicular trafficking. Curr. Biol. 11, 601–607 (2001).Shows that HH signalling is regulated by the transport of vesicles (see also reference 103).
  Article CAS PubMed Google Scholar
• Strutt, H. et al. Mutations in the sterol-sensing domain of Patched suggest a role for vesicular trafficking in Smoothened regulation. Curr. Biol. 11, 608–613 (2001).
  Article CAS PubMed Google Scholar
• Eggenschwiler, J. T., Espinoza, E. & Anderson, K. V. Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway. Nature 412, 194–198 (2001).Highlights the presence of inhibitors of SHH signalling in the dorsal neural tube, as well as the regulation of SHH diffusion/signalling by vesicular components.
  Article CAS PubMed Google Scholar
• Incardona, J. P. et al. Receptor-mediated endocytosis of soluble membrane-tethered Sonic hedgehog by Patched-1. Proc. Natl Acad. Sci. USA 97, 12044–12049 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Huang, Z. & Kunes, S. Hedgehog, transmitted along retinal axons, triggers neurogenesis in the developing visual centers of the Drosophila brain. Cell 86, 411–422 (1996).Shows that HH can be transported through axons to affect target cells.
  Article CAS PubMed Google Scholar
• Wallace, V. A. & Raff, M. C. A role for Sonic hedgehog in axon-to-astrocyte signalling in the rodent optic nerve. Development 126, 2901–2909 (1999).
  Article CAS PubMed Google Scholar
• Traiffort, E., Moya, K. L., Faure, H., Hässig, R. & Ruat, M. High expression and anterograde axonal transport of animo terminal sonic hedgehog in the adult hamster brain. Eur. J. Neurosci. 14, 839–850 (2001).
  Article CAS PubMed Google Scholar
• Ramirez-Weber, F. A. & Kornberg, T. B. Cytonemes: cellular processes that project to the principal signaling center in Drosophila imaginal discs. Cell 97, 599–607 (1999).Cytonemes as an alternative to morphogens for long-range action of signalling molecules.
  Article CAS PubMed Google Scholar
• Dale, J. K. et al. Cooperation of BMP7 and SHH in the induction of forebrain ventral midline cells by prechordal mesoderm. Cell 90, 257–269 (1997).
  Article CAS PubMed Google Scholar
• Liem, K. F. Jr, Tremml, G., Roelink, H. & Jessell, T. M. Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm. Cell 82, 969–979 (1995).An elegant demonstration that BMPs control dorsal differentiation in the early neural tube.
  Article CAS PubMed Google Scholar
• Zuniga, A., Haramis, A. P., McMahon, A. P. & Zeller, R. Signal relay by BMP antagonism controls the SHH/FGF4 feedback loop in vertebrate limb buds. Nature 401, 598–602 (1999).
  Article CAS PubMed Google Scholar
• Rodriguez Esteban, C. et al. The novel Cer-like protein Caronte mediates the establishment of embryonic left–right asymmetry. Nature 401, 243–251 (1999).
  Article CAS PubMed Google Scholar
• Yokouchi, Y., Vogan, K. J., Pearse, R. V. & Tabin, C. J. Antagonistic signaling by Caronte, a novel Cerberus-related gene, establishes left–right asymmetric gene expression. Cell 98, 573–583 (1999).
  Article CAS PubMed Google Scholar
• Liem, K. F. Jr Jessell, T. M. & Briscoe, J. Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites. Development 127, 4855–4866 (2000).
  Article CAS PubMed Google Scholar
• Liu, F., Massague, J. & Ruiz i Altaba, A. Carboxy-terminally truncated Gli3 proteins associate with Smads. Nature Genet. 20, 325–326 (1998).
  Article CAS PubMed Google Scholar
• Ohlmeyer, J. T. & Kalderon, D. Hedgehog stimulates maturation of Cubitus interruptus into a labile transcriptional activator. Nature 396, 749–753 (1998).Evidence that HH is required to make a labile Ci activator in flies. The nature of the modifications that make this activator remain unknown.
  Article CAS PubMed Google Scholar
• Zhu, G., Mehler, M. F., Zhao, J., Yu Yung, S. & Kessler, J. A. Sonic hedgehog and BMP2 exert opposing actions on proliferation and differentiation of embryonic neural progenitor cells. Dev. Biol. 215, 118–129 (1999).
  Article CAS PubMed Google Scholar
• Li, W. & LoTurco, J. J. Noggin is a negative regulator of neuronal differentiation in developing neocortex. Dev. Neurosci. 22, 68–73 (2000).
  Article PubMed Google Scholar
• Panchision, D. M. et al. Sequential actions of BMP receptors control neural precursor cell production and fate. Genes Dev. 15, 2094–2110 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Kawai, S. & Sugiura, T. Characterization of human bone morphogenetic protein (BMP)-4 and -7 gene promoters: activation of BMP promoters by Gli, a sonic hedgehog mediator. Bone 29, 54–61 (2001).
  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).
  Article PubMed Google Scholar
• Grove, E. A., Tole, S., Limon, J., Yip, L. & Ragsdale, C. W. The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in _Gli3_-deficient mice. Development 125, 2315–2325 (1998).
  Article CAS PubMed Google Scholar
• Lee, S. M., Tole, S., Grove, E. & McMahon, A. P. A local Wnt-3a signal is required for development of the mammalian hippocampus. Development 127, 457–467 (2000).
  Article CAS PubMed Google Scholar
• Ragsdale, C. W. & Grove, E. A. Patterning the mammalian cerebral cortex. Curr. Opin. Neurobiol. 11, 50–58 (2001).
  Article CAS PubMed Google Scholar
• Kim, A. S., Lowenstein, D. H. & Pleasure, S. J. Wnt receptors and Wnt inhibitors are expressed in gradients in the developing telencephalon. Mech. Dev. 103, 167–172 (2001).
  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).
  Article CAS PubMed Google Scholar
• Brault, V. et al. Inactivation of the β-catenin gene by _Wnt1_–_Cre_-mediated deletion results in dramatic brain malformation and failure of craniofacial development. Development 128, 1253–1264 (2001).
  Article CAS PubMed Google Scholar
• Chuang, P. T. & McMahon, A. P. Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein. Nature 397, 617–621 (1999).Identification of Hip as a negative regulator of HH signalling.
  Article CAS PubMed 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).
  Article CAS PubMed Google Scholar
• Jiang, F., Frederick, T. J. & Wood, T. L. IGF-I synergizes with FGF-2 to stimulate oligodendrocyte progenitor entry into the cell cycle. Dev. Biol. 232, 414–423 (2001).
  Article CAS PubMed Google Scholar
• Calaora V. et al. Neuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro. J. Neurosci. 21, 4740–4751 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Suh, J., Lu, N., Nicot, A., Tatsuno, I. & DiCicco-Bloom, E. PACAP is an anti-mitogenic signal in developing cerebral cortex. Nature Neurosci. 4, 123–124 (2001).
  Article CAS PubMed Google Scholar
• Waschek, J. A. et al. Neural tube expression of pituitary adenylate cyclase-activating peptide (PACAP) and receptor: potential role in patterning and neurogenesis. Proc. Natl Acad. Sci. USA 95, 9602–9607 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Pons, S. & Marti, E. Sonic hedgehog synergizes with the extracellular matrix protein vitronectin to induce spinal motor neuron differentiation. Development 127, 333–342 (2000).Highlights the importance of the extracellular matrix in the control of SHH signalling.
  Article CAS PubMed Google Scholar
• Lee, C. S., Buttitta, L. & Fan, C. M. Evidence that the WNT-inducible growth arrest-specific gene 1 encodes an antagonist of sonic hedgehog signaling in the somite. Proc. Natl Acad. Sci. USA 98, 11347–11352 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Mullor, J. L. & Ruiz i Altaba, A. Growth, hedgehog and the price of Gas. Bioessays (in the press).
• Huh, S., Hatini, V., Marcus, R. C., Li, S. C. & Lai, E. Dorsal–ventral patterning defects in the eye of BF-1-deficient mice associated with a restricted loss of shh expression. Dev. Biol. 211, 53–63 (1999).
  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).
  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).Reports a mouse model of medulloblastoma.
  Article CAS PubMed Google Scholar