The seven-transmembrane receptor smoothened cell-autonomously induces multiple ventral cell types

Nat Neurosci. 2000 Jan;3(1):41-6. doi: 10.1038/71114.

Abstract

Sonic Hedgehog (Shh) is a secreted protein that controls cell fate and mitogenesis in the developing nervous system. Here we show that a constitutively active form of Smoothened (Smo-M2) mimics concentration-dependent actions of Shh in the developing neural tube, including activation of ventral marker genes (HNF3beta, patched, Nkx2.2, netrin-1), suppression of dorsal markers (Pax-3, Gli-3, Ephrin A5) and induction of ventral neurons (dopaminergic, serotonergic) and ventrolateral motor neurons (Islet-1+, Islet-2+, HB9+) and interneurons (Engrailed-1+, CHX10+). Furthermore, Smo-M2's patterning activities were cell autonomous, occurring exclusively in cells expressing Smo-M2. These findings suggest that Smo is a key signaling component in the Hh receptor and that Shh patterns the vertebrate nervous system as a morphogen, rather than through secondary relay signals.

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Antigens, Differentiation / metabolism
  • Body Patterning / genetics
  • Body Patterning / physiology*
  • Brain / cytology
  • Brain / embryology
  • Brain / metabolism
  • Chick Embryo
  • Embryo, Mammalian
  • Embryonic Induction*
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Hedgehog Proteins
  • Homeobox Protein Nkx-2.2
  • Interneurons / cytology
  • Interneurons / metabolism
  • Mice
  • Mice, Transgenic
  • Motor Neurons / cytology
  • Motor Neurons / metabolism
  • Neural Crest / cytology
  • Neural Crest / embryology*
  • Neural Crest / metabolism
  • Proteins / physiology
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Cell Surface / physiology*
  • Receptors, G-Protein-Coupled*
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Smoothened Receptor
  • Spinal Cord / cytology
  • Spinal Cord / embryology
  • Trans-Activators*
  • Transfection

Substances

  • Antigens, Differentiation
  • Hedgehog Proteins
  • Homeobox Protein Nkx-2.2
  • Nkx2-2 protein, mouse
  • Proteins
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Smo protein, mouse
  • Smoothened Receptor
  • Trans-Activators