Elsevier

Developmental Biology

Volume 427, Issue 1, 1 July 2017, Pages 121-130
Developmental Biology

Original research article
Non-muscle myosin II deletion in the developing kidney causes ureter-bladder misconnection and apical extrusion of the nephric duct lineage epithelia

https://doi.org/10.1016/j.ydbio.2017.04.020Get rights and content
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Highlights

  • Myosin II deletion in the developing kidney causes hydronephrosis.

  • Nephric duct dilatations and ectopic ureteric budding occur at mid-gestation.

  • Apical extrusion and basal protrusion of the epithelia underlie the defects.

  • The phenotypes are caused in a Ret-independent mechanism.

Abstract

In kidney development, connection of the nephric duct (ND) to the cloaca and subsequent sprouting of the ureteric bud (UB) from the ND are important for urinary exit tract formation. Although the roles of Ret signaling are well established, it remains unclear how intracellular cytoskeletal proteins regulate these morphogenetic processes. Myh9 and Myh10 encode two different non-muscle myosin II heavy chains, and Myh9 mutations in humans are implicated in congenital kidney diseases. Here we report that ND/UB lineage-specific deletion of Myh9/Myh10 in mice caused severe hydroureter/hydronephrosis at birth. At mid-gestation, the mutant ND/UB epithelia exhibited aberrant basal protrusion and ectopic UB formation, which likely led to misconnection of the ureter to the bladder. In addition, the mutant epithelia exhibited apical extrusion followed by massive apoptosis in the lumen, which could be explained by reduced apical constriction and intercellular adhesion mediated by E-cadherin. These phenotypes were not ameliorated by genetic reduction of the tyrosine kinase receptor Ret. In contrast, ERK was activated in the mutant cells and its chemical inhibition partially ameliorated the phenotypes. Thus, myosin II is essential for maintaining the apicobasal integrity of the developing kidney epithelia independently of Ret signaling.

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