Multiple functions for the catenin family member plakoglobin in cadherin-dependent adhesion, fibronectin matrix assembly andXenopusgastrulation movements

Abstract

Shaping an embryo requires tissue-scale cell rearrangements known as morphogenetic events. These force-dependent processes require cells to adhere to their neighbors, through cadherin-catenin complexes, and to their extracellular matrix substrates, through integrin-based focal contacts. Integrin receptors are not only important for attachment to the extracellular matrix, but also for its fibrillar assembly.Fibrillogenesis requires actomyosin contractility, regulated in part by cadherin-catenin complexes. One such catenin, plakoglobin, mediates the attachment of actin stress fibers to cadherin cytoplasmic tails through its interactions with actin-binding proteins. In Xenopus gastrulae, plakoglobin has been identified as an essential member in the forceinduced collective migration of the mesendoderm tissue. In the current study, we have further characterized the role of plakoglobin in two additional morphogenetic processes, epiboly and convergent extension. Plakoglobin-deficient tadpoles are 40% shorter and gastrulae contain notochords that are 60% wider than stage-matched controls, indicating convergent extension defects. The radially intercalating ectoderm of morphant animal caps is nearly twice as thick as controls. Furthermore, morphant embryos exhibit a failure to assemble a fibronectin matrix at the notochord-somite-boundary or along the blastocoel roof. The loss of the fibronectin matrix, while not due to changes in overall patterning, is a result of a failure to assemble the soluble dimers into long fibrils. The force of attachment to a cadherin or fibronectin substrate is reduced in plakoglobin morphants, indicating defects in adhesion to both cadherin and fibronectin. These data suggest that plakoglobin regulates morphogenesis and fibronectin assembly through cellcell and cell-matrix adhesion.

The mesodermal source of fibronectin is required for heart morphogenesis and cardiac outflow tract elongation by regulating cell shape, polarity, and mechanotransduction in the second heart field

“…In Xenopus Laevis embryos, disruption of cadherin-mediated adhesions interferes with Fn1 fibrillogenesis, resulting in tissue thickening and the shortening of the anterior-posterior axis due to defects in cell shape, intercellular intercalations, and convergent extension (Dzamba et al, 2009; Hirsh et al, 2018; Weber et al, 2011). Conversely, disruption of Fn1 fibrillogenesis in fish and frog embryos leads to defective planar cell polarity, cell shape, cadherin-mediated adhesion, and cell intercalation (Garavito-Aguilar et al, 2010; Marsden and DeSimone, 2001; Marsden and DeSimone, 2003; Rozario et al, 2009; Trinh and Stainier, 2004; Trinh et al, 2005).…”

“…Disruption of Fn1 fibrillogenesis in zebrafish and Xenopus Laevis embryos leads to defective planar cell polarity, cell shape, cadherin-mediated adhesion, and cell intercalation (Garavito-Aguilar et al, 2010; Kraft-Sheleg et al, 2016; Lackner et al, 2013; Marsden and DeSimone, 2001; Marsden and DeSimone, 2003; Rozario et al, 2009; Trinh and Stainier, 2004; Trinh et al, 2005). Conversely, disruption of cadherin-mediated adhesions in developing Xenopus embryos, interferes with Fn1 fibrillogenesis, resulting in tissue thickening and the shortening of the anterior-posterior axis due to defects in cell shape, intercellular intercalations, and convergent extension (Dzamba et al, 2009; Hirsh et al, 2018; Weber et al, 2011). Our data are consistent with these findings, indicating an indelible evolutionary-conserved role of Fn1 in the crosstalk between cell-cell and cell-ECM adhesions during tissue morphogenesis.…”