Nonmuscle myosin II generates forces that transmit tension and drive contraction in multiple tissues during dorsal closure.
BACKGROUND
The morphogenic movements that characterize embryonic development require the precise temporal and spatial control of cell-shape changes. Drosophila dorsal closure is a well-established model for epithelial sheet morphogenesis, and mutations in more than 60 genes cause defects in closure. Closure requires that four forces, derived from distinct tissues, be precisely balanced. The proteins responsible for generating each of the forces have not been determined.


RESULTS
We document dorsal closure in living embryos to show that mutations in nonmuscle myosin II (encoded by zipper; zip/MyoII) disrupt the integrity of multiple tissues during closure. We demonstrate that MyoII localization is distinct from, but overlaps, F-actin in the supracellular purse string, whereas in the amnioserosa and lateral epidermis each has similar, cortical distributions. In zip/MyoII mutant embryos, we restore MyoII function either ubiquitously or specifically in the leading edge, amnioserosa, or lateral epidermis and find that zip/MyoII function in any one tissue can rescue closure. Using a novel, transgenic mosaic approach, we establish that contractility of the supracellular purse string in leading-edge cells requires zip/MyoII-generated forces; that zip/MyoII function is responsible for the apical contraction of amnioserosa cells; that zip/MyoII is important for zipping; and that defects in zip/MyoII contractility cause the misalignment of the lateral-epidermal sheets during seam formation.


CONCLUSIONS
We establish that zip/MyoII is responsible for generating the forces that drive cell-shape changes in each of the force-generating tissues that contribute to closure. This highly conserved contractile protein likely drives cell-sheet movements throughout phylogeny.
Franke
Josef D
JD
Department of Biology, Developmental Cell and Molecular Biology Group, Duke University, Durham, North Carolina 27708, USA.
Montague
Ruth A
RA
Kiehart
Daniel P
DP
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D001696:Biomechanical Phenomena; D019521:Body Patterning / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000502:physiology*; D024462:Myosin Type II / Q000502:physiology*; D017422:Sequence Analysis, DNA
D029721:Drosophila Proteins; D008565:Membrane Proteins; C097862:Zip protein, Drosophila; D049452:Green Fluorescent Proteins; D024462:Myosin Type II; D018995:Myosin Heavy Chains