Sonic Hedgehog Signalling in Dorsal Midline and Neural Development

Part of the Molecular Biology Intelligence Unit book series (MBIU)


Sonic hedgehog is a secreted morphogen involved in patterning of a variety of structures and organs in vertebrates. In this chapter we focus on its role in the development of the floor plate and in the events that pattern and configure the shape and size of the central nervous system.


Neural Tube Sonic Hedgehog Neural Plate Floor Plate Dorsal Midline 
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  1. 1.
    Lee JJ, von Kessler DP, Parks S et al. Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog. Cell 1992;71:33–50.PubMedCrossRefGoogle Scholar
  2. 2.
    Riddle RD, Johnson RL, Laufer E et al. Sonic hedgehog mediates the polarizing activity of the ZPA. Cell 1993;75:1401–1416.PubMedCrossRefGoogle Scholar
  3. 3.
    Echelard Y, Epstein DJ, St-Jacques B et al. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell 1993;75:1417–1430.PubMedCrossRefGoogle Scholar
  4. 4.
    Krauss S, Concordet JP, Ingham PW. A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos. Cell 1993;75:1431–1444.PubMedCrossRefGoogle Scholar
  5. 5.
    Ekker SC, McGrew LL, Lai CJ et al. Distinct expression and shared activities of members of the hedgehog gene family of Xenopus laevis. Development 1995;121:2337–2347.PubMedGoogle Scholar
  6. 6.
    McMahon AP. More surprises in the Hedgehog signaling pathway. Cell 2000;21:185–188.CrossRefGoogle Scholar
  7. 7.
    Nybakken K, Perrimon N. Hedgehog signal transduction: Recent findings. Curr Opin Genet Dev 2002;12:503–511.PubMedCrossRefGoogle Scholar
  8. 8.
    Nusse R. Wnts and Hedgehogs: Lipid-modified proteins and similarities in signaling mechanisms at the cell surface. Development 2003;130:5297–5305.PubMedCrossRefGoogle Scholar
  9. 9.
    Ruiz i Altaba A, Nguyen V, Palma V. The emergent design of the neural tube: Prepattern, SHH morphogen and GLI code. Curr Opin Genet Dev 2003;13:513–521.PubMedCrossRefGoogle Scholar
  10. 10.
    Briscoe J. Hedgehog signaling: Measuring ligand concentrations with receptor ratios. Curr Biol 2004; 14:R889–R891.PubMedCrossRefGoogle Scholar
  11. 11.
    Tanabe Y, Jessell TM. Diversity and pattern in the developing spinal cord. Science 1996;274:1115–1123.PubMedCrossRefGoogle Scholar
  12. 12.
    Colamarino SA, Tessier-Lavigne M. The role of the floor plate in axon guidance. Annu Rev Neurosci 1995;18:497–529.PubMedCrossRefGoogle Scholar
  13. 13.
    Stoeckli ET, Landmesser LT. Axon guidance at choice points. Curr Opin Neurobiol 1998;8:73–79.PubMedCrossRefGoogle Scholar
  14. 14.
    Rowitch DH, S-Jacques B, Lee SM et al. Sonic hedgehog regulates proliferation and inhibits differentiation of CNS precursor cells. J Neurosci 1999;19:8954–8965.PubMedGoogle Scholar
  15. 15.
    Wechsler-Reya RJ, Scott MP. Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron 1999;22:103–114.PubMedCrossRefGoogle Scholar
  16. 16.
    Charrier JB, Lapointe F, Le Douarin NM et al. Anti-apoptotic role of Sonic hedgehog protein at the early stages of nervous system organogenesis. Development 2001;128:4011–4020.PubMedGoogle Scholar
  17. 17.
    Charrier JB, Lapointe F, Le Douarin et al. Dual origin of the floor plate in the avian embryo. Development 2002;129:4785–4796.PubMedGoogle Scholar
  18. 18.
    Strähle U, Lam CS, Ertzer R et al. Vertebrate floor-plate specification: Variations on common themes. Trends Genet 2004;20:155–162.PubMedCrossRefGoogle Scholar
  19. 19.
    Graham V, Khudyakov J, Ellis P et al. SOX2 functions to maintain neural progenitor identity. Neuron 2003;39:749–765.PubMedCrossRefGoogle Scholar
  20. 20.
    Briscoe J, Sussel L, Serup P et al. Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. Nature 1999;398:622–627.PubMedCrossRefGoogle Scholar
  21. 21.
    Soula C, Danesin C, Kan P 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 2001;128:1369–1379.PubMedGoogle Scholar
  22. 22.
    Qi Y, Cai J, Wu Y et al. Control of oligodendrocyte differentiation by the Nkx2.2 homeodomain transcription factor. Development 2001;128:2723–2733.PubMedGoogle Scholar
  23. 23.
    Le Douarin NM, Halpern ME. Discussion point. Origin and specification of the neural tube floor plate: Insights from the chick and zebrafish. Curr Opin Neurobiol 2000;10:23–30.PubMedCrossRefGoogle Scholar
  24. 24.
    Placzek M, Dodd J, Jessell TM. Discussion point. The case for floor plate induction by the notochord. Curr Opin Neurobiol 2000;10:15–22.PubMedCrossRefGoogle Scholar
  25. 25.
    Roelink H, Augsburger A, Heemskerk J et al. Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord. Cell 1994;76:761–775.PubMedCrossRefGoogle Scholar
  26. 26.
    Roelink H, Porter JA, Chiang C et al. Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis. Cell 1995;81:445–455.PubMedCrossRefGoogle Scholar
  27. 27.
    Marti E, Bumcrot DA, Takada R et al. Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants. Nature 1995;375:322–325.PubMedCrossRefGoogle Scholar
  28. 28.
    Ericson J, Morton S, Kawakami A et al. Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity. Cell 1996;87:661–673.PubMedCrossRefGoogle Scholar
  29. 29.
    Ericson J, Rashbass P, Schedl A et al. Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling. Cell 1997;90:169–180.PubMedCrossRefGoogle Scholar
  30. 30.
    Chiang C, Litingtung Y, Lee E et al. Cydopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 1996;383:407–413.PubMedCrossRefGoogle Scholar
  31. 31.
    Chen W, Burgess S, Hopkins N. Analysis of the zebrafish smoothened mutant reveals conserved and divergent functions of hedgehog activity. Development 2001;128:2385–2396.PubMedGoogle Scholar
  32. 32.
    Varga ZM, Amores A, Lewis KE et al. Zebrafish smoothened functions in ventral neural tube specification and axon tract formation. Development 2001;128:3497–3509.PubMedGoogle Scholar
  33. 33.
    Spemann H, Mangold H. Über Induktion von Embryonalanlagen durch Implantation artfremder Organisatoren. Arch f mikr Anat u Entw Mech 1924;100:599–638.CrossRefGoogle Scholar
  34. 34.
    Shih J, Fraser SE. Distribution of tissue progenitors within the shield region of the zebrafish gastrula. Development 1995;121:2755–2765.PubMedGoogle Scholar
  35. 35.
    Melby AE, Warga RM, Kimmel CB. Specification of cell fates at the dorsal margin of the zebrafish gastrula. Development 1996;122:2225–2237.PubMedGoogle Scholar
  36. 36.
    Charrier JB, Teillet MA, Lapointe F et al. Defining subregions of Hensen’s node essential for caudalward movement, midline development and cell survival. Development 1999;126:4771–4783.PubMedGoogle Scholar
  37. 37.
    Appel B, Fritz A, Westerfield M et al. Delta-mediated specification of midline cell fates in zebrafish embryos. Curr Biol 1999;9:247–256.PubMedCrossRefGoogle Scholar
  38. 38.
    López SL, Paganelli AR, Rosato-Siri MV et al. Notch activates sonic hedgehog and both are involved in the specification of dorsal midline cell-fates in Xenopus. Development 2003;130:2225–2238.PubMedCrossRefGoogle Scholar
  39. 39.
    Halpern ME, Hatta K, Amacher SL et al. Genetic interactions in zebrafish midline development. Dev Biol 1997;187:154–170.PubMedCrossRefGoogle Scholar
  40. 40.
    Teillet MA, Lapointe F, Le Douarin NM. The relationships between notochord and floor plate in vertebrate development revisited. Proc Natl Acad Sci USA 1998;95:11733–11738.PubMedCrossRefGoogle Scholar
  41. 41.
    Epstein DJ, McMahon AP, Joyner AL. Regionalization of Sonic hedgehog transcription along the anteroposterior axis of the mouse central nervous system is regulated by Hnf3-dependent and-independent mechanisms. Development 1999;126:281–292.PubMedGoogle Scholar
  42. 42.
    Jeong Y, Epstein DJ. Distinct regulators of Shh transcription in the floor plate and notochord indicate separate origins for these tissues in the mouse node. Development 2003;130:3891–3902.PubMedCrossRefGoogle Scholar
  43. 43.
    Sulik K, Dehart DB, Iangaki T et al. Morphogenesis of the murine node and notochordal plate. Dev Dyn 1994;201:260–278.PubMedGoogle Scholar
  44. 44.
    Wilson V, Beddington RS. Cell fate and morphogenetic movement in the late mouse primitive streak. Mech Dev 1996;55:79–89.PubMedCrossRefGoogle Scholar
  45. 45.
    Przemeck GK, Heinzmann U, Beckers J et al. Node and midline defects are associated with left-right development in Deltal mutant embryos. Development 2003;130:3–13.PubMedCrossRefGoogle Scholar
  46. 46.
    Patten I, Kulesa P, Shen MM et al. Distinct modes of floor plate induction in the chick embryo. Development 2003;130:4809–4821.PubMedCrossRefGoogle Scholar
  47. 47.
    Patten I, Placzek M. Opponent activities of Shh and BMP signaling during floor plate induction in vivo. Curr Biol 2002;12:47–52.PubMedCrossRefGoogle Scholar
  48. 48.
    Lopez SL, Rosato-Siri MV, Franco PG et al. The Notch-target gene hairy-2a impedes the involution of notochord cells promoting floor plate fates in Xenopus embryos. Development 2005;132(5):1035–46.PubMedCrossRefGoogle Scholar
  49. 49.
    Jessell TM. Neuronal specification in the spinal cord: Inductive signals and transcriptional codes. Nat Rev Genet 2000;1:20–29.PubMedCrossRefGoogle Scholar
  50. 50.
    Briscoe J, Pierani A, Jessell TM et al. A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube. Cell 2000;101:435–445.PubMedCrossRefGoogle Scholar
  51. 51.
    Appel B, Eisen JS. Retinoids run rampant: Multiple roles during spinal cord and motor neuron development. Neuron 2003;40:461–464.PubMedCrossRefGoogle Scholar
  52. 52.
    Wijgerde M, McMahon JA, Rule M et al. A direct requirement for Hedgehog signaling for normal specification of all ventral progenitor domains in the presumptive mammalian spinal cord. Genes Dev 2002;16:2849–2864.PubMedCrossRefGoogle Scholar
  53. 53.
    Bai CB, Stephen D, Joyner AL. All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of GH3. Dev Cell 2004;6:103–115.PubMedCrossRefGoogle Scholar
  54. 54.
    Pierani A, Brenner-Morton S, Chiang C et al. A sonic hedgehog-independent, retinoid-activated pathway of neurogenesis in the ventral spinal cord. Cell 1999;97:903–915.PubMedCrossRefGoogle Scholar
  55. 55.
    Kaellen B. Proliferation in the embryonic brain with special reference to the overgrowth phenomenon an its possible relationship to neoplasia. Prog Brain Res 1965;14:263–278.PubMedCrossRefGoogle Scholar
  56. 56.
    Britto J, Tannahill D, Keynes R. A critical role for sonic hedgehog signaling in the early expansion of the developing brain. Nat Neurosci 2002;5:103–110.PubMedCrossRefGoogle Scholar
  57. 57.
    Ahlgren SC, Bronner-Fraser M. Inhibition of sonic hedgehog signaling in vivo results in craniofacial neural crest cell death. Curr Biol 1999;9:1304–1314.PubMedCrossRefGoogle Scholar
  58. 58.
    Borycki AG, Brunk B, Tajbakhsh S et al. Sonic hedgehog controls epaxial muscle determination through Myf5 activation. Development 1999;126:4053–4063.PubMedGoogle Scholar
  59. 59.
    Ellis HM, Horvitz HR. Genetic control of programmed cell death in the nematode C. elegans. Cell 1986;44:817–829.PubMedCrossRefGoogle Scholar
  60. 60.
    Thibert C, Teillet MA, Lapointe F et al. Inhibition of neuroepithelial patched-induced apoptosis by sonic hedgehog. Science 2003;301:843–846.PubMedCrossRefGoogle Scholar
  61. 61.
    Franco PG, Paganelli AR, López SL et al. Functional association of retinoic acid and hedgehog signaling in Xenopus primary neurogenesis. Development 1999;126:4257–4265.PubMedGoogle Scholar
  62. 62.
    Paganelli AR, Ocana OH, Prat MI et al. The Alzheimer-related gene presenilin-1 facilitates sonic hedgehog expression in Xenopus primary neurogenesis. Mech Dev 2001;107:119–131.PubMedCrossRefGoogle Scholar
  63. 63.
    Dahmane N, Ruiz i Altaba A. Sonic hedgehog regulates the growth and patterning of the cerebellum. Development 1999;126:3089–3100.PubMedGoogle Scholar
  64. 64.
    Dahmane N, Sánchez P, Gitton Y et al. The Sonic Hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis. Development 2001;128:5201–5212.PubMedGoogle Scholar
  65. 65.
    Palma V, Ruiz i Altaba A. Hedgehog-Gli signaling regulates the behaviour of cells with stem cell properties in the developing neocortex. Development 2003;131:337–345.PubMedCrossRefGoogle Scholar
  66. 66.
    Lai K, Kaspar BK, Gage FH et al. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat Neurosci 2003;6:21–27.PubMedCrossRefGoogle Scholar
  67. 67.
    Machold R, Hayashi S, Rutlin M et al. Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron 2003;39:937–950.PubMedCrossRefGoogle Scholar
  68. 68.
    Alvarez-Buylla A, Lim DA. For the long run: Maintaining germinal niches in the adult brain. Neuron 2004;41:683–686.PubMedCrossRefGoogle Scholar
  69. 69.
    Kempermann G, Jessberger S, Steiner B et al. Milestones of neuronal development in the adult hippocampus. Trends Neurosci 2004;27:447–452.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2006

Authors and Affiliations

  1. 1.Laboratorio de Embriologá Molecular, Instituto de Biologá Celular y Neurociencias, Facultad de MedicinaUniversidad de Buenos Aires - CONICETCiudad Autónoma de Buenos AiresArgentina

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