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Reciprocal Spatiotemporally Controlled Apoptosis Regulates Wolffian Duct Cloaca Fusion.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2018 Mar; Vol. 29 (3), pp. 775-783. Date of Electronic Publication: 2018 Jan 11. - Publication Year :
- 2018
-
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 PLC γ 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.<br /> (Copyright © 2018 by the American Society of Nephrology.)
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Animals
Cell Cycle Proteins
Cloaca abnormalities
Cloaca metabolism
Kidney embryology
MAP Kinase Signaling System
Mice
Mutation
Phosphoproteins genetics
Proto-Oncogene Proteins c-ret metabolism
Ureter embryology
Wolffian Ducts abnormalities
Wolffian Ducts metabolism
YAP-Signaling Proteins
Apoptosis genetics
Cloaca embryology
Extracellular Signal-Regulated MAP Kinases metabolism
Proto-Oncogene Proteins c-ret genetics
Urogenital Abnormalities genetics
Wolffian Ducts embryology
Subjects
Details
- Language :
- English
- ISSN :
- 1533-3450
- Volume :
- 29
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 29326158
- Full Text :
- https://doi.org/10.1681/ASN.2017040380