Notch directly regulates cell morphogenesis genes, Reck, talin and trio, in adult muscle progenitors

Abstract

There is growing evidence that Notch pathway activation can result in consequences on cell morphogenesis and behaviour, both during embryonic development and cancer progression. In general, Notch is proposed to co-ordinate these processes by regulating expression of key transcription factors. However, many Notch-regulated genes identified in genome-wide studies are involved in fundamental aspects of cell behaviour, suggesting a more direct influence on cellular properties. By testing the functions of 25 such genes we confirmed that 12 are required in developing adult muscles consistent with roles downstream of Notch. Focusing on three, Reck, rhea/talin and trio, we verify their expression in adult muscle progenitors and identify Notch-regulated enhancers in each. Full activity of these enhancers requires functional binding sites for Su(H), the DNA-binding transcription factor in the Notch pathway, validating their direct regulation. Thus, besides its well-known roles in regulating the expression of cell-fate determining transcription factors, Notch signalling also has the potential to directly affect cell morphology/behaviour by modulating expression of genes such as Reck, rhea/talin and trio. This sheds new light on functional outputs of Notch activation in morphogenetic processes.