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.

Notch Signaling in Vascular Endothelial Cells, Angiogenesis, and Tumor Progression: An Update and Prospective

“…For example, Notch signaling plays different roles during the normal development of different cell types in the pancreas. The Notch pathway plays a pivotal role in deciding the fate of progenitor cells as either exocrine cells (acinar/ductal cells) or endocrine cells (Islets of Langerhans) by lateral inhibition ( Hald et al, 2003 ; Ahnfelt-Rønne et al, 2007 ; Kim et al, 2010 ; de Back et al, 2013 ; Pézeron et al, 2014 ; Li et al, 2016 ).…”

Notch Signaling in Pancreatic Development

“…Here, we review the role of the canonical pathway during pancreatic development. Notch-mediated lateral inhibition represents an important conserved mechanism that regulates cell differentiation, cell proliferation and cell survival in stem cells [ 7 , 8 , 9 ]. Abnormalities in Notch signaling have been linked to various syndromes and diseases, including developmental malformation, neurodegenerative diseases, metabolic disorders, and malignant disease [ 10 , 11 , 12 , 13 ].…”

Notch signaling coordinates ommatidial rotation in the Drosophila eye via transcriptional regulation of the EGF-Receptor ligand Argos

“…In recent years, involvement of Notch signaling in morphogenesis has been suggested in various contexts, including Drosophila oogenesis, zebrafish sensory organ development, and human vascular barrier formation 81–83 . These studies also suggest an input from Notch signaling into the cell adhesion and/or cytoskeletal factors, mostly through Notch-mediated transcription of genes that regulate adhesion and cytoskeletal dynamics 84 although a direct input from the Notch receptor into adhesion factors has also been revealed 85 . Overall, the multifaceted involvement of Notch signaling in cellular (re)organization and morphogenesis is becoming increasingly evident.…”