Cell division in tissues enables macrophage infiltration

Migration of cells through diverse tissues is essential for development, immune response and cancer metastasis 1-3. To reach their destination, cells must overcome the resistance imposed by complex microenvironments, composed of neighboring cells and extracellular matrix (ECM)4-6. While migration through pores and tracks in ECM has been well studied 4,5,7, little is known about cellular traversal into confining cell-dense tissues. Here by combining quantitative live imaging with genetic and optogenetic perturbations we identify a crucial role for cell division during cell migration into tissues. We find that normal embryonic invasion by Drosophila macrophages between the ectoderm and mesoderm8,9 absolutely requires division of an epithelial ectodermal cell at the site of entry. Dividing ectodermal cells disassemble ECM attachment formed by Integrin-mediated focal adhesions next to mesodermal cells, allowing macrophages to move their nuclei ahead and invade. Decreasing or increasing the frequency of ectodermal division correspondingly either hinders or promotes macrophage invasion. Reducing the levels of focal adhesion components in the ectoderm allows macrophage entry even in the absence of division. Our study demonstrates the critical importance of division at the entry site to enable in vivo cell invasion by relieving the steric impediment caused by focal adhesions. We thus provide a new perspective on the regulation of cellular movement into tissues.