Universität zu Köln

Kann, Martin, Bae, Eunnyung, Lenz, Maximilian O., Li, Liangji ORCID: 0000-0002-6635-4800, Schumacher, Valerie A., Taglienti, Mary E., Bordeianou, Liliana, Hartwig, Sunny, Rinschen, Markus M., Schermer, Bernhard ORCID: 0000-0002-5194-9000, Benzing, Thomas, Fan, Chen-Ming and Kreidberg, Jordan A. (2015). WT1 targets Gas1 to maintain nephron progenitor cells by modulating FGF signals. Development, 142 (7). S. 1254 - 1267. CAMBRIDGE: COMPANY BIOLOGISTS LTD. ISSN 1477-9129

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Abstract

Development of the metanephric kidney depends on tightly regulated interplay between self-renewal and differentiation of a nephron progenitor cell (NPC) pool. Several key factors required for the survival of NPCs have been identified, including fibroblast growth factor (FGF) signaling and the transcription factor Wilms' tumor suppressor 1 (WT1). Here, we present evidence that WT1 modulates FGF signaling by activating the expression of growth arrest-specific 1 (Gas1), a novel WT1 target gene and novel modulator of FGF signaling. We show that WT1 directly binds to a conserved DNA binding motif within the Gas1 promoter and activates Gas1 mRNA transcription in NPCs. We confirm that WT1 is required for Gas1 expression in kidneys in vivo. Loss of function of GAS1 in vivo results in hypoplastic kidneys with reduced nephron mass due to premature depletion of NPCs. Although kidney development in Gas1 knockout mice progresses normally until E15.5, NPCs show decreased rates of proliferation at this stage and are depleted as of E17.5. Lastly, we show that Gas1 is selectively required for FGF-stimulated AKT signaling in vitro. In summary, our data suggest a model in which WT1 modulates receptor tyrosine kinase signaling in NPCs by directing the expression of Gas1.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kann, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Bae, Eunnyung UNSPECIFIED UNSPECIFIED UNSPECIFIED Lenz, Maximilian O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Liangji UNSPECIFIED orcid.org/0000-0002-6635-4800 UNSPECIFIED Schumacher, Valerie A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Taglienti, Mary E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bordeianou, Liliana UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartwig, Sunny UNSPECIFIED UNSPECIFIED UNSPECIFIED Rinschen, Markus M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermer, Bernhard UNSPECIFIED orcid.org/0000-0002-5194-9000 UNSPECIFIED Benzing, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Fan, Chen-Ming UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreidberg, Jordan A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-408559
DOI:	10.1242/dev.119735
Journal or Publication Title:	Development
Volume:	142
Number:	7
Page Range:	S. 1254 - 1267
Date:	2015
Publisher:	COMPANY BIOLOGISTS LTD
Place of Publication:	CAMBRIDGE
ISSN:	1477-9129
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MAMMALIAN KIDNEY; SELF-RENEWAL; GENE; COOPERATE; MOUSE; QUANTIFICATION; NEPHROGENESIS; POPULATION; ACTIVATION; EXPRESSION Multiple languages Developmental Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40855