Complex crosstalk of Notch and Hedgehog signalling during the development of the central nervous system

The development of the vertebrate central nervous system (CNS) is tightly regulated by many highly conserved cell signalling pathways. These pathways ensure that differentiation and migration events occur in a specific and spatiotemporally restricted manner. Two of these pathways, Notch and Hedgehog (Hh) signalling, have been shown to form a complex web of interaction throughout different stages of CNS development. Strikingly, some processes employ Notch signalling to regulate Hh response, while others utilise Hh signalling to modulate Notch response. Notch signalling functions upstream of Hh response through controlling the trafficking of integral pathway components as well as through modulating protein levels and transcription of downstream transcriptional factors. In contrast, Hh signalling regulates Notch response by either indirectly controlling expression of key Notch ligands and regulatory proteins or directly through transcriptional control of canonical Notch target genes. Here, we review these interactions and demonstrate the level of interconnectivity between the pathways, highlighting context-dependent modes of crosstalk. Since many other developmental signalling pathways are active in these tissues, it is likely that the interplay between Notch and Hh signalling is not only an example of signalling crosstalk but also functions as a component of a wider, multi-pathway signalling network.