Affordable Access

deepdyve-link
Publisher Website

Reciprocal Spatiotemporally Controlled Apoptosis Regulates Wolffian Duct Cloaca Fusion.

Authors
  • Hoshi, Masato1
  • Reginensi, Antoine2
  • Joens, Matthew S3
  • Fitzpatrick, James A J3, 4, 5
  • McNeill, Helen2
  • Jain, Sanjay6, 7
  • 1 Division of Nephrology, Department of Internal Medicine.
  • 2 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. , (Canada)
  • 3 Center for Cellular Imaging.
  • 4 Department of Cell Biology and Physiology.
  • 5 Department of Neuroscience, and.
  • 6 Division of Nephrology, Department of Internal Medicine, [email protected]
  • 7 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri; and.
Type
Published Article
Journal
Journal of the American Society of Nephrology
Publisher
American Society of Nephrology
Publication Date
Mar 01, 2018
Volume
29
Issue
3
Pages
775–783
Identifiers
DOI: 10.1681/ASN.2017040380
PMID: 29326158
Source
Medline
Keywords
License
Unknown

Abstract

The epithelial Wolffian duct (WD) inserts into the cloaca (primitive bladder) before metanephric kidney development, thereby establishing the initial plumbing for eventual joining of the ureters and bladder. Defects in this process cause common anomalies in the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). However, developmental, cellular, and molecular mechanisms of WD-cloaca fusion are poorly understood. Through systematic analysis of early WD tip development in mice, we discovered that a novel process of spatiotemporally regulated apoptosis in WD and cloaca was necessary for WD-cloaca fusion. Aberrant RET tyrosine kinase signaling through tyrosine (Y) 1062, to which PI3K- or ERK-activating proteins dock, or Y1015, to which PLCγ docks, has been shown to cause CAKUT-like defects. Cloacal apoptosis did not occur in RetY1062F mutants, in which WDs did not reach the cloaca, or in RetY1015F mutants, in which WD tips reached the cloaca but did not fuse. Moreover, inhibition of ERK or apoptosis prevented WD-cloaca fusion in cultures, and WD-specific genetic deletion of YAP attenuated cloacal apoptosis and WD-cloacal fusion in vivo Thus, cloacal apoptosis requires direct contact and signals from the WD tip and is necessary for WD-cloacal fusion. These findings may explain the mechanisms of many CAKUT.

Report this publication

Statistics

Seen <100 times