Hedgehog-GLI signaling inFoxd1-positive stromal cells promotes murine nephrogenesis via TGFβ signaling
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Normal kidney function depends on the proper development of the nephron: the functional unit of the kidney. Reciprocal signaling interactions between the stroma and nephron progenitor compartment have been proposed to control nephron development. Here, we show that removal of hedgehog intracellular effector smoothened (Smo-deficient mutants) in the cortical stroma results in an abnormal renal capsule, and an expanded nephron progenitor domain with an accompanying decrease in nephron number via a block in epithelialization. We show that stromal-hedgehog-Smo signaling acts through a GLI3 repressor. Whole-kidney RNA sequencing and analysis of FACS-isolated stromal cells identified impaired TGFβ2 signaling in Smo-deficient mutants. We show that neutralization and knockdown of TGFβ2 in explants inhibited nephrogenesis. In addition, we demonstrate that concurrent deletion of Tgfbr2 in stromal and nephrogenic cells in vivo results in decreased nephron formation and an expanded nephrogenic precursor domain similar to that observed in Smo-deficient mutant mice. Together, our data suggest a mechanism whereby a stromal hedgehog-TGFβ2 signaling axis acts to control nephrogenesis.
Date Issued
2018-07-01
Date Acceptance
2018-05-30
Citation
Development, 2018, 145 (13), pp.dev159947-dev159947
ISSN
0950-1991
Publisher
The Company of Biologists
Start Page
dev159947
End Page
dev159947
Journal / Book Title
Development
Volume
145
Issue
13
Copyright Statement
© 2018. Published by The Company of Biologists Ltd http://www.biologists.com/user-licence-1-1/
Identifier
https://dev.biologists.org/content/145/13/dev159947
Subjects
06 Biological Sciences
11 Medical and Health Sciences
Publication Status
Published
Date Publish Online
2018-06-26