View Program - 63rd Annual Drosophila Research Conference

Cells migrate collectively during embryonic development and cancer metastasis. Determining how groups of cells detect and respond to confined tissue environments in vivo is a major goal. The nucleus, which is generally the stiffest organelle, deforms and sometimes ruptures to move through confined environments. While in vitro, the stiffness of the nucleus impedes movement of single cells through confined spaces, the effects of nuclear stiffness in vivo are unknown. Further, the roles of nuclei in collective cell migration are not clear. Here, we use border cell migration in the fly ovary as an in vivo model to investigate the effects of confined migration on nuclei. We found severe yet transient nuclear deformations occur, particularly in the leading cell, as border cells squeeze through tiny crevices between germline cells, termed nurse cells. These spaces are narrower than even a single border cell nucleus. Leading cells extend protrusions between nurse cells, which may pry open spaces to allow the cluster to traverse. The nucleus in the leading cell deforms as it moves through the neck of the protrusion and restores a more circular shape as the protrusion widens. In contrast, nuclei in the following cells had less dynamic movement and shape changes. These data suggest that nuclei in leading cells may widen protrusions to expand the size of the migration path and allow the cluster to move forward. To experimentally test how nuclei contribute to border cell migration, we investigated nuclear lamins, proteins that assemble into intermediate filaments to structurally support the nucleus. Depletion of the Drosophila B-type lamin, Lam, from the outer motile border cells, but not the inner, nonmotile polar cells, impeded border cell migration. Surprisingly, perturbations of the Drosophila A-type lamin, LamC, did not impair migration. While wildtype border cell clusters normally have one leading protrusion as they migrate, border cells depleted of B-type lamin had multiple, short-lived protrusions, resulting in unproductive cluster movement and failure to progress down the migration path. Further, border cell nuclei depleted of B-type lamins were smaller, formed blebs, and underwent rupture. Together, these data indicate that B-type lamins maintain nuclear structure, and this is required to stabilize the leading protrusion and promote collective cell migration through confined spaces.

Nuclear lamins promote collective cell migration and coordinate protrusion dynamics