Nonmuscle Myosin II Regulates the Morphogenesis of Metanephric Mesenchyme-Derived Immature Nephrons.
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.
['Recuenco|Mariam C|MC|', 'Ohmori|Tomoko|T|', 'Tanigawa|Shunsuke|S|', 'Taguchi|Atsuhiro|A|', 'Fujimura|Sayoko|S|', 'Conti|Mary Anne|MA|', 'Wei|Qize|Q|', 'Kiyonari|Hiroshi|H|', 'Abe|Takaya|T|', 'Adelstein|Robert S|RS|', 'Nishinakamura|Ryuichi|R|']
D000818:Animals D000831:Animals, Newborn D008648:Mesoderm D008810:Mice, Inbred C57BL D009024:Morphogenesis D018995:Myosin Heavy Chains D009399:Nephrons D024507:Nonmuscle Myosin Type IIA D024501:Nonmuscle Myosin Type IIB D020033:Protein Isoforms
kidney development genetics and development pediatric nephrology