title: Nonmuscle Myosin II Regulates the Morphogenesis of Metanephric Mesenchyme-Derived Immature Nephrons.
abstract: The kidney develops from reciprocal interactions between the metanephric mesenchyme and ureteric bud. The mesenchyme transforms into epithelia and forms complicated nephron structures, whereas the ureteric bud extends its pre-existing epithelial ducts. Although the roles are well established for extracellular stimuli, such as Wnt and Notch, it is unclear how the intracellular cytoskeleton regulates these morphogenetic processes. Myh9 and Myh10 encode nonmuscle myosin II heavy chains, and Myh9 mutations in humans are implicated in congenital kidney diseases and focal segmental glomerulosclerosis in adults. Here, we analyzed the roles of Myh9 and Myh10 in the developing kidney. Ureteric bud-specific depletion of Myh9 resulted in no apparent phenotypes, whereas mesenchyme-specific Myh9 deletion caused proximal tubule dilations and renal failure. Mesenchyme-specific Myh9/Myh10 mutant mice died shortly after birth and showed a severe defect in nephron formation. The nascent mutant nephrons failed to form a continuous lumen, which likely resulted from impaired apical constriction of the elongating tubules. In addition, nephron progenitors lacking Myh9/Myh10 or the possible interactor Kif26b were less condensed at midgestation and reduced at birth. Taken together, nonmuscle myosin II regulates the morphogenesis of immature nephrons derived from the metanephric mesenchyme and the maintenance of nephron progenitors. Our data also suggest that Myh9 deletion in mice results in failure to maintain renal tubules but not in glomerulosclerosis.
authors.affiliation: Department of Kidney Development and.
authors.forename: Mariam C
authors.initials: MC
authors.lastname: Recuenco
authors.affiliation: Department of Kidney Development and.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohmori
authors.affiliation: Department of Kidney Development and.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tanigawa
authors.affiliation: Department of Kidney Development and.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Taguchi
authors.affiliation: Liaison Laboratory Research Promotion Center, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan;
authors.forename: Sayoko
authors.initials: S
authors.lastname: Fujimura
authors.affiliation: Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; and.
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Conti
authors.affiliation: Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; and.
authors.forename: Qize
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Abe
authors.affiliation: Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; and.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Adelstein
authors.affiliation: Department of Kidney Development and ryuichi@kumamoto-u.ac.jp.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishinakamura
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D008648:Mesoderm / Q000502:physiology; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D018995:Myosin Heavy Chains / Q000502:physiology*; D009399:Nephrons / Q000196:embryology* / Q000378:metabolism; D024507:Nonmuscle Myosin Type IIA / Q000502:physiology*; D024501:Nonmuscle Myosin Type IIB / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism
chemical_list: C525088:Myh9 protein, mouse; D020033:Protein Isoforms; D024507:Nonmuscle Myosin Type IIA; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains
keywords: genetics and development; kidney development; pediatric nephrology