title: Cdc42 and formin activity control non-muscle myosin dynamics during Drosophila heart morphogenesis.
abstract: During heart formation, a network of transcription factors and signaling pathways guide cardiac cell fate and differentiation, but the genetic mechanisms orchestrating heart assembly and lumen formation remain unclear. Here, we show that the small GTPase Cdc42 is essential for Drosophila melanogaster heart morphogenesis and lumen formation. Cdc42 genetically interacts with the cardiogenic transcription factor tinman; with dDAAM which belongs to the family of actin organizing formins; and with zipper, which encodes nonmuscle myosin II. Zipper is required for heart lumen formation, and its spatiotemporal activity at the prospective luminal surface is controlled by Cdc42. Heart-specific expression of activated Cdc42, or the regulatory formins dDAAM and Diaphanous caused mislocalization of Zipper and induced ectopic heart lumina, as characterized by luminal markers such as the extracellular matrix protein Slit. Placement of Slit at the lumen surface depends on Cdc42 and formin function. Thus, Cdc42 and formins play pivotal roles in heart lumen formation through the spatiotemporal regulation of the actomyosin network.
authors.affiliation: Development, Aging and Regeneration Program, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037.
authors.forename: Georg
authors.initials: G
authors.lastname: Vogler
authors.affiliation: Development, Aging and Regeneration Program, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Development, Aging and Regeneration Program, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Iafe
authors.affiliation: Biological Research Centre, Hungarian Academy of Sciences, Institute of Genetics, H-6726 Szeged, Hungary.
authors.forename: Ede
authors.initials: E
authors.lastname: Migh
authors.affiliation: Biological Research Centre, Hungarian Academy of Sciences, Institute of Genetics, H-6726 Szeged, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Mihály
authors.affiliation: Development, Aging and Regeneration Program, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037 rolf@sbmri.org.
authors.forename: Rolf
authors.initials: R
authors.lastname: Bodmer
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002465:Cell Movement; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology*; D005260:Female; D000080865:Formins; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006321:Heart / Q000196:embryology*; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D009024:Morphogenesis; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000648:ultrastructure; D018995:Myosin Heavy Chains / Q000502:physiology; D024462:Myosin Type II / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C090145:Cdc42 protein, Drosophila; C509803:DAAM protein, Drosophila; D029721:Drosophila Proteins; D000080865:Formins; D008565:Membrane Proteins; C097862:Zip protein, Drosophila; C106890:diaphanous protein, Drosophila; D019204:GTP-Binding Proteins; D024462:Myosin Type II; D018995:Myosin Heavy Chains