Neural stem cells (NSC) are capable to differentiate toward neuronal, astrocytic, oligodendrocytic and glial lineages, depending on their spatial location within the central nervous system. NSC change their characteristics during development: initially they proliferate and then, due to complex signaling cascades give rise first to neurons and then to glial cells. Five key signaling molecules have been postulated to regulate this differentiation pattern: Wnt, FGF (fibroblast growth factor), TGF-β (transforming growth factor β),  Hedgehog and Notch. In all different neuroglial stem cell lines studied thus far, these signaling molecules participate in differentiation. Recent advances in our present understanding of lineage commitment for glial cells, particularly astrocytes and radial glia, indicate that these messengers may play an instructive role in the promotion of glial development.

Wnt signaling is a cell-cell signaling system that operates during development, through a cell surface receptor that blocks degradation of β-catenin and thereby enables it to interact with transcription factors of the TCF/LEF family, modulating transcription of several target genes.  However, two other alternative pathways may involve a rise in intracellular calcium levels and crosstalk with another pathways involving G proteins and kinases as JNK.

In this review, we focus particularly in the role of Wnt pathways in the determination of the radial glial cell fate, making emphasis in the instructive role played by neuron-glial interactions.