Noggin is a negative regulator of neuronal differentiation in developing neocortex

Bone morphogenetic proteins (BMPs) trigger neuronal differentiation of neoc ortical precursors within the ventricular zone (VZ) [Li et al. (1998): J Ne urosci 18:88538862]. BMP-2/4 protein is concentrated at the VZ surface and BMPs rapidly promote the differentiation of neocortical precursors in both dissociated cell and explant cultures. Noggin binds to BMP-2/4 with high af finity, and prevents binding to cell surface receptors. In the present stud y, we used human recombinant noggin protein to determine whether endogenous BMP-2/4 triggers neuronal differentiation in dissociated cell culture. We find that noggin inhibits the differentiation of neocortical neurons: noggi n decreases the number of MAP-2- and TUJ 1positive cells after 24 h of trea tment, yet has no effect on either proliferation or cell survival. Noggin a lso significantly decreases neurite growth of MAP-2-positive cells. In addi tion, using Western blot analysis we show that noggin protein is present in developing cortex at E15. These results are consistent with previous resul ts showing that endogenous BMPs trigger neuronal differentiation in the neo cortical VZ and also indicate that a balance of noggin and BMP may regulate the differentiation of neocortical neurons in vive. CopyrightB 2000 S. Kar ger AG. Basel.