Nance-Horan-syndrome-like 1b controls mesodermal cell migration by regulating protrusion and actin dynamics during...

Cell migrations are crucial for embryonic development, wound healing, the immune response, as well as for cancer progression. During mesenchymal cell migration, the Rac1-WAVE-Arp2/3 signalling pathway induces branched actin polymerisation, which protrudes the membrane and allows migration. Fine-tuning the activity of the Rac1-WAVE-Arp2/3 pathway modulates protrusion lifetime and migration persistence. Recently, NHSL1, a novel interactor of the Scar/WAVE complex has been identified as a negative regulator of cell migration in vitro. We here analysed its function in vivo, during zebrafish gastrulation, when nhsl1b is expressed in migrating mesodermal cells. Loss and gain of function experiments revealed that nhsl1b is required for the proper migration of the mesoderm, controlling cell speed and migration persistence. Nhsl1b localises to the tip of actin-rich protrusions where it controls protrusion dynamics, its loss of function reducing the length and lifetime of protrusions, whereas overexpression has the opposite effect. Within the protrusion, Nhsl1b knockdown increases F-actin assembly rate and retrograde flow. These results identify Nhsl1b as a cell type specific regulator of cell migration and highlight the importance of analysing the function of regulators of actin dynamics in physiological contexts.