Rho-Kinase Directs Bazooka/Par-3 Planar Polarity during Drosophila Axis Elongation

Abstract

Summary Cell rearrangements shape the Drosophila embryo through spatially regulated changes in cell shape and adhesion. We show that Bazooka/Par-3 (Baz) is required for the planar polarized distribution of myosin II and adherens junction proteins and polarized intercalary behavior is disrupted in baz mutants. The myosin II activator Rho-kinase is asymmetrically enriched at anterior and posterior borders of intercalating cells in a pattern complementary to Baz. Loss of Rho-kinase results in expansion of the Baz domain and activated Rho-kinase is sufficient to exclude Baz from the cortex. The planar polarized distribution of Baz requires its C-terminal domain. Rho-kinase can phosphorylate this domain and inhibit its interaction with phosphoinositide membrane lipids, suggesting a mechanism by which Rho-kinase could regulate Baz association with the cell cortex. These results demonstrate that Rho-kinase plays an instructive role in planar polarity by targeting Baz/Par-3 and myosin II to complementary cortical domains.

Par3/Bazooka and phosphoinositides regulate actin protrusion formation during Drosophila dorsal closure and wound healing

“…As depletion of PIP3 did not block actomyosin cable assembly, loss of Baz must also trigger a PIP3-independent pathway that drives cable assembly. Baz exhibits a reciprocal distribution to actomyosin in other processes in the Drosophila embryo, including germband extension and amnioserosa remodelling; however, the molecular basis of this reciprocal relationship is not well understood, although recent work has indicated that Rho-kinase is involved (Pope and Harris, 2008;Simões et al, 2010;Zallen and Wieschaus, 2004).…”

The roles and regulation of multicellular rosette structures during morphogenesis

“…Elongation is reduced in embryos deficient for myosin-II heavy chain, myosin regulatory light chain (MRLC), Rok, which activates MRLC, or Shroom (Bertet et al, 2004;Simões et al, 2010Simões et al, , 2014. Furthermore, disruption of Par-3, Par-6 or aPKC also impairs elongation (Blankenship et al, 2006;Simões et al, 2010;Zallen and Wieschaus, 2004), potentially due to roles for these proteins in rosette formation. In addition, microtubules are important for the asymmetric localization of a mobile E-cadherin pool and Par-3 complex (Bulgakova et al, 2013).…”

“…It is crucial for the processes of gastrulation, neurulation and organogenesis, all of which require multicellular rearrangements such as tissue elongation. In certain contexts, the planar polarized distribution of molecules involved in acto-myosin constriction and cell adhesion can give rise to rosette formation (Blankenship et al, 2006;Lienkamp et al, 2012;Simões et al, 2010;Tamada et al, 2012). In a subset of these cases, molecules involved in the planar cell polarity (PCP) pathway, including noncanonical Wnt, are clearly required for rosette formation (Lienkamp et al, 2012).…”

“…Intercalating cells in the epithelium initially establish planar polarity, which is first identifiable by the asymmetric enrichment of F-actin at the AP borders between cells (Blankenship et al, 2006). Myosin-II and its activator Rho kinase (Rok, a homolog of Rock) also accumulate at AP borders and promote localized junctional contraction (Bertet et al, 2004;Zallen and Wieschaus, 2004;Simões et al, 2010) and, recently, the scaffolding protein Shroom was shown to be required for Rok and myosin-II junctional activation, downstream of Rok signaling (Simões et al, 2014). Subsequently, AJs, as assayed by staining for β-catenin (Armadillo) and E-cadherin (Shotgun), become enriched (Haas and Gilmour, 2006; modified with permission from Harding and Nechiporuk, 2012).…”

Myosin II is not required for Drosophila tracheal branch elongation and cell intercalation

“…S1), whether intercalation per se is the driving force leading to branch extension remains debatable. Several studies in epithelial tissues suggest that intercalation is the direct consequence of increased cortical contractility resulting from the dynamics and the localization of MyoII, thereby generating the major force controlling tissue elongation (Bardet et al, 2013;Bertet et al, 2004;Rauzi et al, 2008;Simoes et al, 2010). However, external forces acting on tissue boundaries have also been implicated in tissue elongation.…”