Defining the Role of Integrins in Melanoblast Migration In Vivo

During embryonic development, neural crest-derived melanoblasts, which are precursors of pigment-producing melanocytes, disperse throughout the skin by long-range cell migration that requires adhesion to the ECM. Members of the integrin family of cell-ECM adhesion receptors are thought to contribute to melanocyte migration in vitro. However, due to the functional redundancy between different integrin heterodimers, the precise role of integrins in melanoblast migration, as well as the mechanisms that regulate them in this process, especially in in vivo contexts, remain poorly understood. To address this, we utilize the existing transcriptomic databases to identify different integrin subunits that are specifically expressed in melanoblasts, melanocytes and melanoma cancer cell lines. We then use mouse embryonic skin explants combined with drug and small molecule-based perturbations to target different integrins as well as specific mechanisms that modulate integrin activity. Individual melanoblasts from live imaging movies are tracked using high-resolution, quantitative, automated analysis, and cell morphology, cell migration and actin-based protrusions are analyzed. Overall, we uncover the non-redundant roles of different integrin heterodimers and elucidate the function of outside-in integrin activation in melanoblasts. Finally, we describe the function played, in vivo, by integrin-mediated adhesion to specific ECM ligands during melanoblast migration. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]