Neuronal heterotopias in the developing cerebral cortex produced by neurotrophin-4.
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.
Brunstrom
J E
JE
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Gray-Swain
M R
MR
Osborne
P A
PA
Pearlman
A L
AL
D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D002465:Cell Movement / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D002828:Choristoma / Q000139:chemically induced* / Q000196:embryology / Q000473:pathology; D006801:Humans; D007276:Injections, Intraventricular; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D009024:Morphogenesis / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology* / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects / Q000235:genetics / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; C073922:neurotrophin 4