SAX-7/L1CAM and HMR-1/cadherin function redundantly in blastomere compaction and non-muscle myosin accumulation during Caenorhabditis elegans gastrulation

Abstract

Gastrulation is the first major morphogenetic movement in development, and requires dynamic regulation of cell adhesion and the cytoskeleton. C. elegans gastrulation begins with the migration of the two endodermal precursors, Ea and Ep, from the surface of the embryo into the interior. Ea/Ep migration provides a relatively simple system to examine the intersection of cell adhesion, cell signaling, and cell movement. Ea/Ep ingression depends on correct cell fate specification and polarization, apical myosin accumulation, and Wnt activated actomyosin contraction that drives apical constriction and ingression (Lee et al., 2006; Nance et al., 2005). Here, we show that Ea/Ep ingression also requires the function of either HMR-1/cadherin or SAX-7/L1CAM. Both cadherin complex components and L1CAM are localized at all sites of cell-cell contact during gastrulation. Either system is sufficient for Ea/Ep ingression, but loss of both together leads to a failure of apical constriction and ingression. Similar results are seen with isolated blastomeres. Ea/Ep are properly specified and appear to display correct apical-basal polarity in sax-7(eq1); hmr-1(RNAi) embryos. Significantly, in sax-7(eq1); hmr-1(RNAi) embryos Ea and Ep fail to accumulate myosin (NMY-2::GFP) at their apical surfaces, but in either sax-7(eq1) or hmr-1(RNAi) embryos, apical myosin accumulation is comparable to wildtype. Thus, the cadherin and L1CAM adhesion systems are redundantly required for localized myosin accumulation, and hence for actomyosin contractility during gastrulation. We also show that sax-7 and hmr-1 function are redundantly required for Wnt-dependent spindle polarization during division of the ABar blastomere, indicating that these cell surface proteins redundantly regulate multiple developmental events in early embryos.

L1-Mediated Colon Cancer Cell Metastasis Does Not Require Changes in EMT and Cancer Stem Cell Markers

“…The current studies with CRC cells while further supporting an increase in cell motility induced by L1, did not observe concomitant changes in E-cadherin in a variety of CRC cell lines, or in the more motile and invasive CRC cells of the human tumor tissue front. In Caenorhabditis elegans, the L1 homologue SAX-7 and E-cadherin play a redundant role during development and can substitute for each other (29). These 2 molecules, however, do not completely colocalize and their organization and expression is not affected when either one of the molecules is genetically eliminated (29).…”

“…In Caenorhabditis elegans, the L1 homologue SAX-7 and E-cadherin play a redundant role during development and can substitute for each other (29). These 2 molecules, however, do not completely colocalize and their organization and expression is not affected when either one of the molecules is genetically eliminated (29). Our results are consistent with this independence in the 2 adhesive systems mediated by L1 and Ecadherin and the lack of influence on their expression when the level of either of the molecules is altered.…”

Development and Cell Polarity of the C. elegans Intestine

“…The CeAJ is a belt-like junctional structure that encircles the apex of polarized epithelial cells and resembles the ZA in other systems. By immunohistochemistry, the apicolateral membrane domain can be subdivided into four subdomains (Fig.6): the PPC together with the Drosophila Crumbs homolog CRB-1 and the multi PDZ-domain containing protein MAGI-1 (Achilleos et al, 2010;Aono et al, 2004;Bossinger et al, 2001;Stetak and Hajnal, 2011;Totong et al, 2007), the catenin-cadherin complex (CCC; Costa et al, 1998;Grana et al, 2010;Kwiatkowski et al, 2010), the DLG-1-AJM-1 complex (DAC; Bossinger et al, 2001;Firestein and Rongo, 2001;Köppen et al, 2001;Lockwood et al, 2008;McMahon et al, 2001) and the LET-413 protein Legouis et al, 2000;Legouis et al, 2003;Lockwood et al, 2008;Pilipiuk et al, 2009;Segbert et al, 2004).…”

“…HMR-1/E-cadherin + SAX-7/L1CAM (Hoffmann et al, in preparation), HMP-1/ -catenin + DLG-1 , or HMR-1/cadherin + ERM-1 give rise to intestinal cell-cell adhesion defects. HMR-1/E-cadherin and SAX-7/L1CAM also function redundantly in blastomere compaction and non-muscle myosin accumulation during C. elegans gastrulation (Grana et al, 2010). Interestingly, early embryonic and epithelial cells lacking PAR-6 can separate from one another inappropriately (Nance, 2003;Totong et al, 2007).…”

“…The ingression of Ea and Ep cells depends on correct cell fate specification and polarization of the machinery that orchestrates cell shape changes and cell migration (Lee and Goldstein, 2003;Sawyer et al, 2011). Among these, PAR-3 and PAR-6 proteins regulate apical accumulation of myosin heavy chain, and a Wnt-Frizzled signaling pathway modulates contraction of the actomyosin network that drives apical constriction and finally leads to correct ingression of endodermal precursor cells (Cabello et al, 2010;Grana et al, 2010;Lee et al, 2006). Gastrulation in C. elegans later continues with the internalization of other cells including mesoderm and germline progenitors (Chisholm and Hardin, 2005;Nance et al, 2005).…”