Induction of midbrain dopaminergic neurons by Sonic hedgehog

Neuron. 1995 Jul;15(1):35-44. doi: 10.1016/0896-6273(95)90062-4.


Midbrain dopaminergic neurons, whose loss in adults results in Parkinson's disease, can be specified during embryonic development by a contact-dependent signal from floor plate cells. Here we show that the amino-terminal product of Sonic hedgehog autoproteolysis (SHH-N), an inductive signal expressed by floor plate cells, can induce dopaminergic neurons in vitro. We show further that manipulations to increase the activity of cyclic AMP-dependent protein kinase A, which is known to antagonize hedgehog signaling, can block dopaminergic neuron induction by floor plate cells. Our results and those of other studies indicate that SHH-N can function in a dose-dependent manner to induce different cell types within the neural tube. Our results also provide the basis for a potential cell transplantation therapy for Parkinson's disease.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured / metabolism
  • Culture Media
  • Cyclic AMP-Dependent Protein Kinases / agonists
  • Dopamine / physiology*
  • Embryonic Induction / physiology*
  • Hedgehog Proteins
  • In Situ Hybridization
  • Mesencephalon / cytology*
  • Mesencephalon / metabolism
  • Mice
  • Neurons / metabolism*
  • Peptide Fragments / metabolism
  • Proteins / isolation & purification
  • Proteins / metabolism*
  • Proteins / pharmacology
  • Rats
  • Recombinant Proteins / metabolism
  • Trans-Activators*


  • Culture Media
  • Hedgehog Proteins
  • Peptide Fragments
  • Proteins
  • Recombinant Proteins
  • Trans-Activators
  • Cyclic AMP-Dependent Protein Kinases
  • Dopamine