ROBO2 restricts the nephrogenic field and regulates Wolffian duct-nephrogenic cord separation

Wainwright, Elanor N., Wilhelm, Dagmar, Combes, Alexander N., Little, Melissa H. and Koopman, Peter (2015) ROBO2 restricts the nephrogenic field and regulates Wolffian duct-nephrogenic cord separation. Developmental Biology, 404 2: 88-102. doi:10.1016/j.ydbio.2015.05.023

Author Wainwright, Elanor N.
Wilhelm, Dagmar
Combes, Alexander N.
Little, Melissa H.
Koopman, Peter
Title ROBO2 restricts the nephrogenic field and regulates Wolffian duct-nephrogenic cord separation
Journal name Developmental Biology   Check publisher's open access policy
ISSN 1095-564X
Publication date 2015-08-15
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.ydbio.2015.05.023
Open Access Status Not yet assessed
Volume 404
Issue 2
Start page 88
End page 102
Total pages 15
Place of publication Maryland Heights, MO United States
Publisher Academic Press
Collection year 2016
Language eng
Formatted abstract
ROBO2 plays a key role in regulating ureteric bud (UB) formation in the embryo, with mutations in humans and mice leading to supernumerary kidneys. Previous studies have established that the number and position of UB outgrowths is determined by the domain of metanephric mesenchymal Gdnf expression, which is expanded anteriorly in Robo2 mouse mutants. To clarify how this phenotype arises, we used high-resolution 3D imaging to reveal an increase in the number of nephrogenic cord cells, leading to extension of the metanephric mesenchyme field in Robo2-null mouse embryos. Ex vivo experiments suggested a dependence of this effect on proliferative signals from the Wolffian duct. Loss of Robo2 resulted in a failure of the normal separation of the mesenchyme from the Wolffian duct/ureteric epithelium, suggesting that aberrant juxtaposition of these two compartments in Robo2-null mice exposes the mesenchyme to abnormally high levels of proliferative stimuli. Our data suggest a new model in which SLIT-ROBO signalling acts not by attenuating Gdnf expression or activity, but instead by limiting epithelial/mesenchymal interactions in the nascent metanephros and restricting the extent of the nephrogenic field. These insights illuminate the aetiology of multiplex kidney formation in human individuals with ROBO2 mutations.
Keyword Kidney
Wolffian duct
Ureteric bud
Nephrogenic cord
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
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