NEURONAL DIFFERENTIATION OF PRECURSORS IN THE NEOCORTICAL VENTRICULARZONE IS TRIGGERED BY BMP

Neocortical neurons begin to differentiate soon after they are generat ed by mitoses at the surface of the ventricular zone (VZ). We provide evidence here that bone morphogenetic protein (BMP) triggers neuronal differentiation of neocortical precursors within the VZ. In cultures o f dissociated neocortical neuroepithelial cells, BMPs increase the num ber of MAP-2- and TUJ1-positive cells within 24 hr of treatment. In ex plant cultures, BMP-4 treatment leads to an increase in the number of TUJ1- positive cells within the ventricular zone. Furthermore, truncat ed, dominant-negative, BMP type I receptor, introduced into neocortica l precursors by retrovirus-mediated gene transfer, blocks neurite elab oration and migration out of the VZ. Finally, immunocytochemistry indi cates that BMP protein is present at the VZ surface. Together, these r esults indicate that BMP protein is present within the VZ, that BMP is capable of promoting neuronal differentiation, and that signaling thr ough BMP receptors triggers neuronal precursors to differentiate and m igrate out of the VZ.