Roles for Cell Adhesion During Zebrafish Muscle Morphogenesis

The dynamic nature of interactions between cells and their environment is a fundamental aspect of developmental biology and physiological homeostasis. Both cell‐cell and cell‐matrix adhesion change continuously in response to a myriad of molecular and biophysical signals. Understanding how these interactions mediate specific cell behaviors is crucial to understanding tissue structure generation during development and how these behaviors are coopted during disease. We have identified a novel regulator of cell‐matrix adhesion, Nicotinamide Riboside Kinase 2b (Nrk2b). Nrk2b promotes laminin organization at the nascent MTJ during zebrafish muscle development. Nrk2b‐mediated NAD+ production is also sufficient to reduce muscle degeneration in a zebrafish model of muscular dystrophy by 2–10 fold. Although we do not yet know the mechanism of NAD+ action, downstream proteins include ADP ribosyltransferase 1/4 and Integrin a6. Nrk2b also genetically interacts with two major modulators of cell‐cell adhesion, N‐ and M‐cadherin. In summary, Nrk2b is an important upstream regulator of multiple adhesion complexes, thus playing a critical role in mediating cellular interactions with the microenvironment. Funding: NICHD.