PgmNr Z6049: The requirement of cell-matrix interactions for planar cell polarity and convergence and extension
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Authors:
A. Love; J. Jessen


Institutes
Middle Tennessee State University, Murfreesboro, TN.


Abstract:

Integral to convergence and extension movements during development, the planar cell polarity (PCP) pathway is a non-canonical Wnt pathway that regulates the coordinated movement of cells within a tissue plane. During zebrafish gastrulation, defects in core PCP proteins such as Vangl2, encoded by the trilobite gene, result in failed convergence and extension cell movements. As a result, vangl2/trilobite mutant embryos have hallmark phenotypes, including a shortened and broadened dorsal body axis.  Previous work from the Solnica-Krezel lab showed that mesodermal cells in vangl2/trilobite mutant embryos do not follow the intended path of collective migration to the dorsal axis for proper embryonic development, instead these cells lack directionality. In other work, the Jessen lab demonstrated that vangl2/trilobite mutant embryos also exhibit an increase in matrix metalloproteinase activity and a decrease in the extracellular matrix (ECM) protein fibronectin. Given that cells in vangl2/trilobite mutant embryos are characterized as having inappropriate membrane protrusive activity, we hypothesize that these embryos have defective cell-matrix interactions necessary for proper protrusion formation. Integrins are transmembrane receptors for many ECM proteins, including perhaps the most prevalent ECM protein in the zebrafish gastrula, fibronectin. Integrins control dynamic interactions between the cell’s actin cytoskeleton and its surrounding matrix. It is well known that mesenchymal cell migration begins with protrusion at the leading edge, adhesion to ECM, and stabilization; at which time, cell body movement occurs as the rear cell adhesions are released. Using whole-mount in situ hybridization and confocal microscopy, we are characterizing the relationship between cell-matrix interactions and the PCP pathway. We have shown that vangl2/trilobite mutant embryos are sensitive to loss of integrins a5, aV, and b1 function. Moreover, we find that loss of fibronectin in vangl2/trilobite mutant embryos results in only a subtly enhanced convergence and extension phenotype, indicative of decreased sensitivity to loss of fibronectin. These preliminary results are consistent with the notion that vangl2/trilobite mutants have decreased total fibronectin. Ongoing experiments address the effects of disrupted cell-matrix interactions on the establishment of planar cell polarity at the cellular level.



ZFIN Genetics Index
1. tri
2. vangl2
3. fn1
4. fn1b
5. itga1
6. itgb1
7. itgb3
8. itgav