Abstract
Cell migration and polarization is controlled by signals in the environment. Migrating cells typically form filopodia that extend from the cell surface, but the precise function of these structures in cell polarization and guided migration is poorly understood. Using the in vivo model of zebrafish primordial germ cells for studying chemokine-directed single cell migration, we show that filopodia distribution and their dynamics are dictated by the gradient of the chemokine Cxcl12a. By specifically interfering with filopodia formation, we demonstrate for the first time that these protrusions play an important role in cell polarization by Cxcl12a, as manifested by elevation of intracellular pH and Rac1 activity at the cell front. The establishment of this polarity is at the basis of effective cell migration towards the target. Together, we show that filopodia allow the interpretation of the chemotactic gradient in vivo by directing single-cell polarization in response to the guidance cue.
Highlights
Cell migration is essential for tissue and organ development, for tissue homeostasis and function
To define the mechanisms that could contribute to the apparent polarity of migrating Primordial germ cells (PGCs), we first measured the distribution of Cxcr4b on the cell membrane around the cell perimeter
A 10 min time-lapse video of a PGC in medNY054 homozygous embryo knocked down for Cxcr7b and that expresses uniform levels of Cxcl12a-encoding RNA was captured using a 63× objective on a Zeiss AxioImager.M2 microscope equipped with a Photometrics camera (Cascade II) and VS
Summary
Cell migration is essential for tissue and organ development, for tissue homeostasis and function. It has been proposed that filopodia transport signalling molecules to neighbouring cells (Sanders et al, 2013; Roy et al, 2014), promote adhesion and are important for generation of traction forces (Albuschies and Vogel, 2013; Fierro-Gonzalez et al, 2013) and serve as a sensing organelle (reviewed in [Wood and Martin, 2002]) The latter notion arose from functional studies that were carried out in vitro and involved manipulations that could have affected different processes in addition to filopodia formation in chemotrophic growth cones (Zheng et al, 1996; Rajnicek et al, 2006).
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