title: A self-organized biomechanical network drives shape changes during tissue morphogenesis.
abstract: Tissue morphogenesis is orchestrated by cell shape changes. Forces required to power these changes are generated by non-muscle myosin II (MyoII) motor proteins pulling filamentous actin (F-actin). Actomyosin networks undergo cycles of assembly and disassembly (pulses) to cause cell deformations alternating with steps of stabilization to result in irreversible shape changes. Although this ratchet-like behaviour operates in a variety of contexts, the underlying mechanisms remain unclear. Here we investigate the role of MyoII regulation through the conserved Rho1-Rok pathway during Drosophila melanogaster germband extension. This morphogenetic process is powered by cell intercalation, which involves the shrinkage of junctions in the dorsal-ventral axis (vertical junctions) followed by junction extension in the anterior-posterior axis. While polarized flows of medial-apical MyoII pulses deform vertical junctions, MyoII enrichment on these junctions (planar polarity) stabilizes them. We identify two critical properties of MyoII dynamics that underlie stability and pulsatility: exchange kinetics governed by phosphorylation-dephosphorylation cycles of the MyoII regulatory light chain; and advection due to contraction of the motors on F-actin networks. Spatial control over MyoII exchange kinetics establishes two stable regimes of high and low dissociation rates, resulting in MyoII planar polarity. Pulsatility emerges at intermediate dissociation rates, enabling convergent advection of MyoII and its upstream regulators Rho1 GTP, Rok and MyoII phosphatase. Notably, pulsatility is not an outcome of an upstream Rho1 pacemaker. Rather, it is a self-organized system that involves positive and negative biomechanical feedback between MyoII advection and dissociation rates.
authors.affiliation: Aix Marseille Université, CNRS, IBDM UMR7288, 13009 Marseille, France.
authors.forename: Akankshi
authors.initials: A
authors.lastname: Munjal
authors.affiliation: Aix Marseille Université, CNRS, IBDM UMR7288, 13009 Marseille, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Philippe
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Edwin
authors.initials: E
authors.lastname: Munro
authors.affiliation: Aix Marseille Université, CNRS, IBDM UMR7288, 13009 Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lecuit
mesh_terms: D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D016764:Cell Polarity; D048430:Cell Shape; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D005260:Female; D007700:Kinetics; D008297:Male; D009024:Morphogenesis; D018994:Myosin Light Chains / Q000378:metabolism; D024462:Myosin Type II / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D010766:Phosphorylation; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D018994:Myosin Light Chains; D000205:Actomyosin; D054460:rho-Associated Kinases; C495592:Mbs protein, Drosophila; D043263:Myosin-Light-Chain Phosphatase; D024462:Myosin Type II; D020741:rho GTP-Binding Proteins