ABSTRACT
The phenomenon of tissue fluidity-cells' ability to rearrange relative to each other in confluent tissues-has been linked to several morphogenetic processes and diseases, yet few molecular regulators of tissue fluidity are known. Ommatidial rotation (OR), directed by planar cell polarity signaling, occurs during Drosophila eye morphogenesis and shares many features with polarized cellular migration in vertebrates. We utilize in vivo live imaging analysis tools to quantify dynamic cellular morphologies during OR, revealing that OR is driven autonomously by ommatidial cell clusters rotating in successive pulses within a permissive substrate. Through analysis of a rotation-specific nemo mutant, we demonstrate that precise regulation of junctional E-cadherin levels is critical for modulating the mechanical properties of the tissue to allow rotation to progress. Our study defines Nemo as a molecular tool to induce a transition from solid-like tissues to more viscoelastic tissues broadening our molecular understanding of tissue fluidity.
Subject(s)
Adherens Junctions , Cell Polarity , Extracellular Fluid , Adherens Junctions/genetics , Adherens Junctions/metabolism , Animals , Cadherins , Cell Polarity/genetics , Cell Polarity/physiology , Drosophila/genetics , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Ectoderm , Eye/cytology , Mitogen-Activated Protein Kinases/genetics , Mitogen-Activated Protein Kinases/metabolism , Morphogenesis , Wings, Animal/cytologyABSTRACT
The presence of DNA double-strand breaks during mitosis is particularly challenging for the cell, as it produces broken chromosomes lacking a centromere. This situation can cause genomic instability resulting from improper segregation of the broken fragments into daughter cells. We recently uncovered a process by which broken chromosomes are faithfully transmitted via the BubR1-dependent tethering of the two broken chromosome ends. However, the mechanisms underlying BubR1 recruitment and function on broken chromosomes were largely unknown. We show that BubR1 requires interaction with Bub3 to localize on the broken chromosome fragments and to mediate their proper segregation. We also find that Cdc20, a cofactor of the E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C), accumulates on DNA breaks in a BubR1 KEN box-dependent manner. A biosensor for APC/C activity demonstrates a BubR1-dependent local inhibition of APC/C around the segregating broken chromosome. We therefore propose that the Bub3-BubR1 complex on broken DNA inhibits the APC/C locally via the sequestration of Cdc20, thus promoting proper transmission of broken chromosomes.
Subject(s)
Cdc20 Proteins/metabolism , Cell Cycle Proteins/metabolism , Chromosomes/genetics , Diptera/metabolism , Drosophila Proteins/metabolism , Anaphase/genetics , Anaphase-Promoting Complex-Cyclosome/genetics , Anaphase-Promoting Complex-Cyclosome/metabolism , Animals , Cell Cycle Proteins/genetics , Chromosomes/metabolism , DNA Breaks, Double-Stranded , Diptera/genetics , Drosophila/genetics , Drosophila/metabolism , Drosophila Proteins/genetics , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Spindle Apparatus/genetics , Spindle Apparatus/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
How adhesive contacts with neighbors may affect epithelial cell cytokinesis is unknown. We report that in Drosophila, septins are specifically required for planar (but not orthogonal) cytokinesis. During planar division, cytokinetic furrowing initiates basally, resulting in a contractile ring displaced toward the adherens junction (AJ). The formation of new AJ between daughter cells requires the disengagement of E-Cadherin complexes between mitotic and neighboring cells at the cleavage furrow, followed by the assembly of E-Cadherin complexes on the daughter-daughter interface. The strength of adhesion with neighbors directly impacts both the kinetics of AJ disengagement and the length of the new AJ. Loss of septins causes a reduction in the contractility of the actomyosin ring and prevents local disengagement of AJ in the cleavage furrow. By modulating the strength of tension induced by neighbors, we uncover a mechanical function for septins to overcome the extrinsic tension induced by neighboring interphasic cells.
Subject(s)
Actomyosin , Adherens Junctions , Cytokinesis/genetics , Septins , Actin Cytoskeleton/genetics , Actin Cytoskeleton/metabolism , Actomyosin/genetics , Actomyosin/metabolism , Adherens Junctions/genetics , Adherens Junctions/physiology , Animals , Cadherins/genetics , Cadherins/metabolism , Cell Adhesion/genetics , Cell Polarity , Drosophila melanogaster/genetics , Drosophila melanogaster/growth & development , Drosophila melanogaster/metabolism , Embryonic Development , Epithelial Cells/cytology , Epithelial Cells/metabolism , Gene Expression Regulation, Developmental , Muscle Contraction/genetics , Septins/genetics , Septins/metabolism , Thorax/cytology , Thorax/growth & developmentABSTRACT
Recent findings report the selective internalization of core planar cell polarity components during mitosis followed by cell-non-autonomous polarized recycling. This novel mechanistic model explains how tissue polarity is inherited in daughter cells of proliferative tissue.
