Development of the urogenital system is regulated via the 3 ' UTR of GDNF

Show full item record



Permalink

http://hdl.handle.net/10138/300972

Citation

Li , H , Jakobson , M , Ola , R , Gui , Y , Kumar , A , Sipilä , P , Sariola , H , Kuure , S & Andressoo , J-O 2019 , ' Development of the urogenital system is regulated via the 3 ' UTR of GDNF ' , Scientific Reports , vol. 9 , 5302 . https://doi.org/10.1038/s41598-019-40457-1

Title: Development of the urogenital system is regulated via the 3 ' UTR of GDNF
Author: Li, Hao; Jakobson, Madis; Ola, Roxana; Gui, Yujuan; Kumar, Anmol; Sipilä, Petra; Sariola, Hannu; Kuure, Satu; Andressoo, Jaan-Olle
Contributor: University of Helsinki, Helsinki Institute of Life Science HiLIFE, Joint Activities
University of Helsinki, Department of Biochemistry and Developmental Biology
University of Helsinki, Department of Biochemistry and Developmental Biology
University of Helsinki, Helsinki Institute of Life Science HiLIFE
University of Helsinki, Hannu Sariola / Principal Investigator
University of Helsinki, Koe-eläinkeskus / Muuntogeeniyksikkö
University of Helsinki, Institute of Biotechnology
Date: 2019-03-28
Language: eng
Number of pages: 14
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/300972
Abstract: Mechanisms controlling ureter lenght and the position of the kidney are poorly understood. Glial cellline derived neurotrophic factor (GDNF) induced RET signaling is critical for ureteric bud outgrowth, but the function of endogenous GDNF in further renal differentiation and urogenital system development remains discursive. Here we analyzed mice where 3' untranslated region (UTR) of GDNF is replaced with sequence less responsive to microRNA-mediated regulation, leading to increased GDNF expression specifically in cells naturally transcribing Gdnf. We demonstrate that increased Gdnf leads to short ureters in kidneys located in an abnormally caudal position thus resembling human pelvic kidneys. High GDNF levels expand collecting ductal progenitors at the expense of ureteric trunk elongation and result in expanded tip and short trunk phenotype due to changes in cell cycle length and progenitor motility. MEK-inhibition rescues these defects suggesting that MAPK-activity mediates GDNF's effects on progenitors. Moreover, Gdnf(hyper) mice are infertile likely due to effects of excess GDNF on distal ureter remodeling. Our findings suggest that dysregulation of GDNF levels, for example via alterations in 3' UTR, may account for a subset of congenital anomalies of the kidney and urinary tract (CAKUT) and/or congenital infertility cases in humans and pave way to future studies.
Subject: NEPHRIC DUCT INSERTION
BRANCHING MORPHOGENESIS
NEUROTROPHIC FACTOR
KIDNEY DEVELOPMENT
RENAL AGENESIS
CELL-PROLIFERATION
VITAMIN-A
RET
FAMILY
ASSOCIATION
1182 Biochemistry, cell and molecular biology
3111 Biomedicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
s41598_019_40457_1.pdf 7.156Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record