Neuronal heterotopias in the developing cerebral cortex produced by neurotrophin-4

Neuron. 1997 Mar;18(3):505-17. doi: 10.1016/s0896-6273(00)81250-7.


The marginal zone (MZ) of embryonic neocortex is crucial to its normal development. We report that neurotrophin-4 (but not NT3 or NGF), applied to embryonic rodent cortex in vitro or in vivo, produces heterotopic accumulations of neurons in the MZ. Although heterotopia production is TrkB mediated, BDNF is >10-fold less effective than NT4. Heterotopic neurons have the same birth date and phenotype as normal MZ neurons; they are not the result of NT4-induced proliferation or rescue from apoptosis. We suggest that NT4 causes excess neurons to migrate into the MZ and thus may play a role in normal MZ formation as well as in the pathogenesis of certain human cortical dysplasias.

Publication types

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

MeSH terms

  • Abnormalities, Drug-Induced / pathology*
  • Animals
  • Apoptosis / drug effects
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Brain-Derived Neurotrophic Factor / toxicity
  • Cell Division / drug effects
  • Cell Lineage
  • Cell Movement / drug effects
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / embryology
  • Cerebral Cortex / pathology
  • Choristoma / chemically induced*
  • Choristoma / embryology
  • Choristoma / pathology
  • Humans
  • Injections, Intraventricular
  • Mice
  • Mice, Inbred C3H
  • Mice, Knockout
  • Morphogenesis / drug effects
  • Nerve Growth Factors / pharmacology*
  • Nerve Growth Factors / toxicity
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / physiology
  • Neurons / drug effects*
  • Organ Culture Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Nerve Growth Factor / drug effects
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / physiology


  • Brain-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Nerve Growth Factor
  • neurotrophin 4