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), appl ied to embryonic rodent cortex in vitro or in vivo, produces heterotop ic accumulations of neurons in the MZ. Although heterotopia production is TrkB mediated, BDNF is >10-fold less effective than NT4. Heterotop ic 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 t he MZ and thus may play a role in normal MZ formation as well as in th e pathogenesis of certain human cortical dysplasias.