BDNF REGULATES REELIN EXPRESSION AND CAJAL-RETZIUS CELL-DEVELOPMENT IN THE CEREBRAL-CORTEX

Cajar-Retzius (CR) cells of the cerebral cortex express receptors for the neurotrophin brain-derived neurotrophic factor (BDNF) and downregu late expression of the extracellular matrix protein Reelin during earl y postnatal development, coincident with the onset of cortical BDNF ex pression. During this period, mice lacking BDNF have elevated levels o f Reelin in CR cells. Acute BDNF stimulation of cortical neuron cultur es and overexpression of BDNF in the developing brain of transgenic mi ce prior to the onset of endogenous production causes a profound, dose -dependent reduction of Reelin expression in CR cells. In addition, ov erexpression of BDNF produces gaps and heterotopias in the marginal zo ne and disorganization and aggregation of cortical CR cells and induce s several other malformations, including aberrant cortical lamination, similar to the phenotype of reeler mutant mice, which lack Reelin. Th ese results demonstrate a role for BDNF on cortical CR cells and ident ify Reelin as a direct effector of this neurotrophin during brain deve lopment.