title: Bazooka inhibits aPKC to limit antagonism of actomyosin networks during amnioserosa apical constriction.
abstract: Cell shape changes drive tissue morphogenesis during animal development. An important example is the apical cell constriction that initiates tissue internalisation. Apical constriction can occur through a phase of cyclic assembly and disassembly of apicomedial actomyosin networks, followed by stabilisation of these networks. Delayed negative-feedback mechanisms typically underlie cyclic behaviour, but the mechanisms regulating cyclic actomyosin networks remain obscure, as do mechanisms that transform overall network behaviour. Here, we show that a known inhibitor of apicomedial actomyosin networks in Drosophila amnioserosa cells, the Par-6-aPKC complex, is recruited to the apicomedial domain by actomyosin networks during dorsal closure of the embryo. This finding establishes an actomyosin-aPKC negative-feedback loop in the system. Additionally, we find that aPKC recruits Bazooka to the apicomedial domain, and phosphorylates Bazooka for a dynamic interaction. Remarkably, stabilising aPKC-Bazooka interactions can inhibit the antagonism of actomyosin by aPKC, suggesting that Bazooka acts as an aPKC inhibitor, and providing a possible mechanism for delaying the actomyosin-aPKC negative-feedback loop. Our data also implicate an increasing degree of Par-6-aPKC-Bazooka interactions as dorsal closure progresses, potentially explaining a developmental transition in actomyosin behaviour from cyclic to persistent networks. This later impact of aPKC inhibition is supported by mathematical modelling of the system. Overall, this work illustrates how shifting chemical signals can tune actomyosin network behaviour during development.
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, M5S 3G5, Canada.
authors.forename: Daryl J V
authors.initials: DJ
authors.lastname: David
authors.forename: Qiming
authors.initials: Q
authors.lastname: Wang
authors.forename: James J
authors.initials: JJ
authors.lastname: Feng
authors.forename: Tony J C
authors.initials: TJ
authors.lastname: Harris
mesh_terms: D000205:Actomyosin / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D016764:Cell Polarity; D048430:Cell Shape; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009024:Morphogenesis; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C400774:baz protein, Drosophila; D000205:Actomyosin; C115015:PKC-3 protein; C532584:Par-6 protein, Drosophila; D011493:Protein Kinase C
keywords: Actomyosin networks; Apical constriction; Par proteins