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1.  Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs 
The Journal of Cell Biology  2009;184(3):399-408.
Epithelial–mesenchymal transition (EMT) is required for mesodermal differentiation during development. The zinc-finger transcription factor, Snail1, can trigger EMT and is sufficient to transcriptionally reprogram epithelial cells toward a mesenchymal phenotype during neoplasia and fibrosis. Whether Snail1 also regulates the behavior of terminally differentiated mesenchymal cells remains unexplored. Using a Snai1 conditional knockout model, we now identify Snail1 as a regulator of normal mesenchymal cell function. Snail1 expression in normal fibroblasts can be induced by agonists known to promote proliferation and invasion in vivo. When challenged within a tissue-like, three-dimensional extracellular matrix, Snail1-deficient fibroblasts exhibit global alterations in gene expression, which include defects in membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invasive activity. Snail1-deficient fibroblasts explanted atop the live chick chorioallantoic membrane lack tissue-invasive potential and fail to induce angiogenesis. These findings establish key functions for the EMT regulator Snail1 after terminal differentiation of mesenchymal cells.
doi:10.1083/jcb.200810113
PMCID: PMC2646556  PMID: 19188491
2.  Mesangial cells organize the glomerular capillaries by adhering to the G domain of laminin α5 in the glomerular basement membrane 
The Journal of Cell Biology  2003;161(1):187-196.
In developing glomeruli, laminin α5 replaces laminin α1 in the glomerular basement membrane (GBM) at the capillary loop stage, a transition required for glomerulogenesis. To investigate domain-specific functions of laminin α5 during glomerulogenesis, we produced transgenic mice that express a chimeric laminin composed of laminin α5 domains VI through I fused to the human laminin α1 globular (G) domain, designated Mr51. Transgene-derived protein accumulated in many basement membranes, including the developing GBM. When bred onto the Lama5 −/− background, Mr51 supported GBM formation, preventing the breakdown that normally occurs in Lama5 −/− glomeruli. In addition, podocytes exhibited their typical arrangement in a single cell layer epithelium adjacent to the GBM, but convolution of glomerular capillaries did not occur. Instead, capillaries were distended and exhibited a ballooned appearance, a phenotype similar to that observed in the total absence of mesangial cells. However, here the phenotype could be attributed to the lack of mesangial cell adhesion to the GBM, suggesting that the G domain of laminin α5 is essential for this adhesion. Analysis of an additional chimeric transgene allowed us to narrow the region of the α5 G domain essential for mesangial cell adhesion to α5LG3-5. Finally, in vitro studies showed that integrin α3β1 and the Lutheran glycoprotein mediate adhesion of mesangial cells to laminin α5. Our results elucidate a mechanism whereby mesangial cells organize the glomerular capillaries by adhering to the G domain of laminin α5 in the GBM.
doi:10.1083/jcb.200211121
PMCID: PMC2172883  PMID: 12682087
mesangium; cell adhesion; kidney glomerulus; integrin α3β1; transgenic mice

Results 1-2 (2)