Receptor Tyrosine Kinase (RTK) Signalling in the Control of Neural Stem and Progenitor Cell (NSPC) Development

Important developmental responses are elicited in neural stem and progenitor cells (NSPC) by activation of the receptor tyrosine kinases (RTK), including the fibroblast growth factor receptors, epidermal growth factor receptor, platelet-derived growth factor receptors and insulin-like growth factor receptor (IGF1R). Signalling through these RTK is necessary and sufficient for driving a number of developmental processes in the central nervous system. Within each of the four RTK families discussed here, receptors are activated by sets of ligands that do not cross-activate receptors of the other three families, and therefore, their activation can be independently regulated by ligand availability. These RTK pathways converge on a conserved core of signalling molecules, but differences between the receptors in utilisation of signalling molecules and molecular adaptors for intracellular signal propagation become increasingly apparent. Intracellular inhibitors of RTK signalling are widely involved in the regulation of developmental signalling in NSPC and often determine developmental outcomes of RTK activation. In addition, cellular responses of NSPC to the activation of a given RTK may be significantly modulated by signal strength. Cellular propensity to respond also plays a role in developmental outcomes of RTK signalling. In combination, these mechanisms regulate the balance between NSPC maintenance and differentiation during development and in adulthood. Attribution of particular developmental responses of NSPC to specific pathways of RTK signalling becomes increasingly elucidated. Co-activation of several RTK in developing NSPC is common, and analysis of co-operation between their signalling pathways may advance knowledge of RTK role in NSPC development.