title: PAR-6, but not E-cadherin and β-integrin, is necessary for epithelial polarization in C. elegans.
abstract: Cell polarity is a fundamental characteristic of epithelial cells. Classical cell biological studies have suggested that establishment and orientation of polarized epithelia depend on outside-in cues that derive from interactions with either neighboring cells or the substratum (Akhtar and Streuli, 2013; Chen and Zhang, 2013; Chung and Andrew, 2008; McNeill et al., 1990; Nejsum and Nelson, 2007; Nelson et al., 2013; Ojakian and Schwimmer, 1994; Wang et al., 1990; Yu et al., 2005). This paradigm has been challenged by examples of epithelia generated in the absence of molecules that mediate cell-cell or cell-matrix interactions, notably E-cadherin and integrins (Baas et al., 2004; Choi et al., 2013; Costa et al., 1998; Harris and Peifer, 2004; Raich et al., 1999; Roote and Zusman, 1995; Vestweber et al., 1985; Williams and Waterston, 1994; Wu et al., 2009). Here we explore an alternative hypothesis, that cadherins and integrins function redundantly to substitute for one another during epithelium formation (Martinez-Rico et al., 2010; Ojakian et al., 2001; Rudkouskaya et al., 2014; Weber et al., 2011). We use C. elegans, which possesses a single E-cadherin (Costa et al., 1998; Hardin et al., 2013; Tepass, 1999) and a single β-integrin (Gettner et al., 1995; Lee et al., 2001), and analyze the arcade cells, which generate an epithelium late in embryogenesis (Portereiko and Mango, 2001; Portereiko et al., 2004), after most maternal factors are depleted. Loss of E-cadherin(HMR-1) in combination with β-integrin(PAT-3) had no impact on the onset or formation of the arcade cell epithelium, nor the epidermis or digestive tract. Moreover, ß-integrin(PAT-3) was not enriched at the basal surface of the arcades, and the candidate PAT-3 binding partner β-laminin(LAM-1) was not detected until after arcade cell polarity was established and exhibited no obvious polarity defect when mutated. Instead, the polarity protein par-6 (Chen and Zhang, 2013; Watts et al., 1996) was required to polarize the arcade cells, and par-6 mutants exhibited mislocalized or absent apical and junctional proteins. We conclude that the arcade cell epithelium polarizes by a PAR-6-mediated pathway that is independent of E-cadherin, β-integrin and β-laminin.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Boston, MA 02138, USA. Electronic address: svonstetina@mcb.harvard.edu.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Von Stetina
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Boston, MA 02138, USA. Electronic address: smango@mcb.harvard.edu.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Mango
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000196:embryology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D015820:Cadherins; D029742:Caenorhabditis elegans Proteins; D039641:Integrin beta Chains; D007797:Laminin; D034741:RNA, Small Interfering; C450060:hmr-1 protein, C elegans; C512642:par-6 protein, C elegans; C093515:pat-3 protein, C elegans
keywords: C. elegans; E-cadherin; Epithelial cell polarity; PAR-6; β-integrin