Neuroglial interactions play a key role in the development of the nervous system. This study investigated the role of synaptic transmitters (glutamate and D-serine) and a trophic factor, transforming growth factor-β1 (TGF-β1), as mediators of these interactions during the differentiation of radial glial cells (neural progenitors) and astrocytes. Our data suggest a possible role for NMDA-type glutamatergic receptors in GR specialization during neuronal migration in the cerebral cortex. We also analyzed the role of glutamate in astrocytic maturation through TGF-β1 pathways. The activation of metabotropic glutamate receptors 2/3 by neurons induces the secretion of TGF-β1, leading to the activation of the GFAP gene and astrocyte maturation. Both the production of TGF-β1 and the activation of the GFAP gene by this factor involve the MAPK/PI3K pathways. Our work shows that glutamatergic receptors are involved in events of cerebral cortex development such as GR specification and astrocyte maturation.