Identification and Regulation of a Molecular Module for Bleb-Based Cell Motility

Abstract

Single-cell migration is a key process in development, homeostasis, and disease. Nevertheless, the control over basic cellular mechanisms directing cells into motile behavior in vivo is largely unknown. Here, we report on the identification of a minimal set of parameters the regulation of which confers proper morphology and cell motility. Zebrafish primordial germ cells rendered immotile by knockdown of Dead end, a negative regulator of miRNA function, were used as a platform for identifying processes restoring motility. We have defined myosin contractility, cell adhesion, and cortex properties as factors whose proper regulation is sufficient for restoring cell migration of this cell type. Tight control over the level of these cellular features, achieved through a balance between miRNA-430 function and the action of the RNA-binding protein Dead end, effectively transforms immotile primordial germ cells into polarized cells that actively migrate relative to cells in their environment.

Rho activation is apically restricted by Arhgap1 in neural crest cells and drives epithelial-to-mesenchymal transition

“…By contrast, blebs contact a very different extracellular environment, including the basal lamina and the ECM of the peripheral mesenchyme, to which cells may adhere and thereby generate traction and forward movement. In primordial germ cells, blebs protrude forward and, as they retract, actomyosin coupled with adhesion pulls the cell forward (Goudarzi et al, 2012;Kardash et al, 2010). Our data are consistent with NCC blebs driving forward movement in a similar manner.…”

Mitotic cell rounding and epithelial thinning regulate lumen growth and shape

“…Bleb formation was previously related to cortical actomyosin tension 26 . The observed 26,27 . Remarkably, in the otic vesicle, the rounding cells are immersed in a packed epithelium, ARTICLE such that the rounding severed cells are pushing over other cells to form the bleb.…”

Hydraulic fracturing in cells and tissues: fracking meets cell biology

“…However, if the cytoskeletal network is dense, a relatively long-lived pressure transient will develop, the cell membrane will detach from the actin cortex, and a bleb will form. Experimental support to this mechanism includes the observation that blebs can be induced by creating local pressure differences using micropipettes [16], by locally reducing the adhesion energy between the cell and its cortex [17], by locally ablating the actin cortex with a laser [18], by increasing cortical contractility [19], and by depolymerizing the cortex [20]. However, establishing a definitive causal link between membrane/cortex facture and a local increase in pressure of poroelastic origin remains a remarkable experimental challenge.…”