BDNF/MAPK/ERK–Induced BMP7 Expression in the Developing Cerebral Cortex Induces Premature Radial Glia Differentiation and Impairs Neuronal Migration

Duringdevelopmentofthemammaliannervoussystem,acombination of genetic and environmental factors governs the sequential generation of neurons and glia and the initial establishment of the neuralcircuitry.Here,wedemonstratethatbrain-derivedneurotrophic factor (BDNF), one of those local acting factors, induces Bone Morphogenetic Protein 7 (BMP7) expression in embryonic neurons by activating Mitogen-Activated Protein Kinase/Extracellular signalRegulated Kinase signaling and by the negative regulation of p53/ p73 function. We also show that intraventricular injection of BMP7 at midgestation induces the early differentiation of radial glia into glial precursors and astrocytes and the expression of mature glial markers such as the antiadhesive protein SC1. As a result of this precocious radial glia maturation, the laminar distribution of late-born pyramidal neuronsisaltered,mostlikelybytheterminationofradialgliaabilityto support neuronal migration and the early neuronal detachment from the glial rail. We propose a mechanism for BDNF regulation of BMP7 in which local activity--driven BDNF-induced BMP7 expression at the end of neurogenesis instructs competent precursors to generate astrocytes. Such a mechanism might ensure synchronic neuronal and glial maturation at the beginning of cortical activity.