Fluid flow and guidance of collective cell migration

Pathology Department, Massachusetts General Hospital, Charlestown, MA, USA.
Cell adhesion & migration (Impact Factor: 4.51). 07/2010; 4(3):353-7. DOI: 10.4161/cam.4.3.11428
Source: PubMed


Collective cell migration is emerging as a significant component of many biological processes including metazoan development, tissue maintenance and repair and tumor progression. Different contexts dictate different mechanisms by which migration is guided and maintained. In vascular endothelia subjected to significant shear stress, fluid flow is utilized to properly orient a migrating group of cells. Recently, we discovered that the developing zebrafish pronephric epithelium undergoes a similar response to luminal fluid flow, which guides pronephric epithelial migration towards the glomerulus. Intratubular migration leads to significant changes in kidney morphology. This novel process provides a powerful in vivo model for further exploration of the mechanisms underlying mechanotransduction and collective migration.

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    • "To our surprise, we did not observe an acute, direct effect of PI3K inhibition on pronephric epithelial migration. This discrepancy may reflect the fact that pronephric epithelial migration takes place in the absence of leading edge, a common feature of most forms of collective migration [27], [28]. In pronephric migration, every migrating epithelial cell has another cell in front of it. "
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    ABSTRACT: Organ development leads to the emergence of organ function, which in turn can impact developmental processes. Here we show that fluid flow-induced collective epithelial migration during kidney nephron morphogenesis induces cell stretch that in turn signals epithelial proliferation. Increased cell proliferation was dependent on PI3K signaling. Inhibiting epithelial proliferation by blocking PI3K or CDK4/Cyclin D1 activity arrested cell migration prematurely and caused a marked overstretching of the distal nephron tubule. Computational modeling of the involved cell processes predicted major morphological and kinetic outcomes observed experimentally under a variety of conditions. Overall, our findings suggest that kidney development is a recursive process where emerging organ function "feeds back" to the developmental program to influence fundamental cellular events such as cell migration and proliferation, thus defining final organ morphology.
    Full-text · Article · Jul 2012 · PLoS ONE
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    ABSTRACT: Kidney function requires the appropriate distribution of membrane proteins between the apical and basolateral surfaces along the kidney tubule. Further, the absolute amount of a protein at the cell surface vs. intracellular compartments must be attuned to specific physiological needs. Endolyn (CD164) is a transmembrane protein that is expressed at the brush border and in apical endosomes of the proximal convoluted tubule and in lysosomes of more distal segments. Endolyn has been shown to regulate CXCR4 signaling in hematopoietic precursor cells and myoblasts; however, little is known about endolyn function in adult or developing kidney. Here we identify endolyn as a novel gene important for zebrafish pronephric kidney function. Zebrafish endolyn lacks the amino terminal mucin-like domain of the mammalian protein, but is otherwise highly conserved. Using in situ hybridization we show that endolyn is expressed early during development in zebrafish brain, eye, gut, and pronephric kidney. Embryos injected with a translation inhibiting morpholino targeted against endolyn developed pericardial edema, hydrocephaly, and body curvature. The pronephric kidney appeared normal morphologically, but clearance of fluorescent dextran injected into the common cardinal vein was delayed, consistent with a defect in the regulation of water balance in morphant embryos. Heterologous expression of rat endolyn rescued the morphant phenotypes. Interestingly, rescue experiments using mutant rat endolyn constructs revealed that both apical sorting and endocytic/lysosomal targeting motifs are required for normal pronephric kidney function. This suggests that both polarized targeting and postendocytic trafficking of endolyn are essential for the protein's proper function in mammalian kidney.
    No preview · Article · Sep 2012 · Journal of Cell Science
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