Noggin Is a Negative Regulator of Neuronal Differentiation in Developing Neocortex

Abstract

Bone morphogenetic proteins (BMPs) trigger neuronal differentiation of neocortical precursors within the ventricular zone (VZ) [Li et al. (1998): J Neurosci 18:8853–8862]. 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 affinity, and prevents binding to cell surface receptors. In the present study, 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: noggin decreases the number of MAP-2- and TUJ1-positive cells after 24 h of treatment, yet has no effect on either proliferation or cell survival. Noggin also significantly decreases neurite growth of MAP-2-positive cells. In addition, using Western blot analysis we show that noggin protein is present in developing cortex at E15. These results are consistent with previous results showing that endogenous BMPs trigger neuronal differentiation in the neocortical VZ and also indicate that a balance of noggin and BMP may regulate the differentiation of neocortical neurons in vivo.