title: Yap- and Cdc42-dependent nephrogenesis and morphogenesis during mouse kidney development.
abstract: Yap is a transcriptional co-activator that regulates cell proliferation and apoptosis downstream of the Hippo kinase pathway. We investigated Yap function during mouse kidney development using a conditional knockout strategy that specifically inactivated Yap within the nephrogenic lineage. We found that Yap is essential for nephron induction and morphogenesis, surprisingly, in a manner independent of regulation of cell proliferation and apoptosis. We used microarray analysis to identify a suite of novel Yap-dependent genes that function during nephron formation and have been implicated in morphogenesis. Previous in vitro studies have indicated that Yap can respond to mechanical stresses in cultured cells downstream of the small GTPases RhoA. We find that tissue-specific inactivation of the Rho GTPase Cdc42 causes a severe defect in nephrogenesis that strikingly phenocopies loss of Yap. Ablation of Cdc42 decreases nuclear localization of Yap, leading to a reduction of Yap-dependent gene expression. We propose that Yap responds to Cdc42-dependent signals in nephron progenitor cells to activate a genetic program required to shape the functioning nephron.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Antoine
authors.initials: A
authors.lastname: Reginensi
authors.forename: Rizaldy P
authors.initials: RP
authors.lastname: Scott
authors.forename: Alex
authors.initials: A
authors.lastname: Gregorieff
authors.forename: Mazdak
authors.initials: M
authors.lastname: Bagherie-Lachidan
authors.forename: Chaeuk
authors.initials: C
authors.lastname: Chung
authors.forename: Dae-Sik
authors.initials: DS
authors.lastname: Lim
authors.forename: Tony
authors.initials: T
authors.lastname: Pawson
authors.forename: Jeff
authors.initials: J
authors.lastname: Wrana
authors.forename: Helen
authors.initials: H
authors.lastname: McNeill
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D007668:Kidney / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000091102:YAP-Signaling Proteins; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C581598:Cdc42 protein, mouse; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D020764:cdc42 GTP-Binding Protein
references.citation: PLoS Genet. 2010 Jan 15;6(1):e1000809
references.pmid: 20084103
references.citation: Nat Rev Cancer. 2007 Mar;7(3):182-91
references.pmid: 17318211
references.citation: Nature. 2011 Jun 08;474(7350):179-83
references.pmid: 21654799
references.citation: Cell. 1999 Apr 16;97(2):221-31
references.pmid: 10219243
references.citation: Mol Cell Biol. 2006 Jan;26(1):77-87
references.pmid: 16354681
references.citation: Curr Opin Cell Biol. 2008 Dec;20(6):638-46
references.pmid: 18955139
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15424-9
references.pmid: 17878299
references.citation: Mol Cell Biol. 2009 Dec;29(23):6309-20
references.pmid: 19786569
references.citation: Annu Rev Cell Dev Biol. 2006;22:509-29
references.pmid: 16822174
references.citation: Cell Stem Cell. 2008 Aug 7;3(2):169-81
references.pmid: 18682239
references.citation: Nat Cell Biol. 2011 Aug 01;13(8):877-83
references.pmid: 21808241
references.citation: Development. 2007 Feb;134(4):801-11
references.pmid: 17229764
references.citation: N Engl J Med. 2003 Jan 9;348(2):101-8
references.pmid: 12519920
references.citation: Development. 2007 Jul;134(13):2533-9
references.pmid: 17537789
references.citation: Am J Physiol Renal Physiol. 2008 Mar;294(3):F542-53
references.pmid: 18172001
references.citation: Dev Cell. 2010 Oct 19;19(4):491-505
references.pmid: 20951342
references.citation: Cell. 2012 Aug 17;150(4):780-91
references.pmid: 22863277
references.citation: Development. 1995 Dec;121(12):4057-65
references.pmid: 8575306
references.citation: Dev Cell. 2012 Apr 17;22(4):695-702
references.pmid: 22516196
references.citation: Dev Cell. 2009 Mar;16(3):398-410
references.pmid: 19289085
references.citation: Cold Spring Harb Perspect Biol. 2012 May 01;4(5):
references.pmid: 22550230
references.citation: Genes Dev. 2010 Jun 1;24(11):1106-18
references.pmid: 20516196
references.citation: Development. 2011 Jan;138(1):9-22
references.pmid: 21138973
references.citation: Development. 2010 Jan;137(2):283-92
references.pmid: 20040494
references.citation: Development. 2011 Sep;138(18):3907-14
references.pmid: 21831922
references.citation: Science. 2011 Apr 22;332(6028):458-61
references.pmid: 21512031
references.citation: Dev Cell. 2005 Aug;9(2):283-92
references.pmid: 16054034
references.citation: Dev Biol. 2009 Aug 15;332(2):273-86
references.pmid: 19501082
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1631-6
references.pmid: 17251353
references.citation: Curr Opin Biotechnol. 1995 Feb;6(1):20-3
references.pmid: 7534503
references.citation: Anat Rec. 1992 Feb;232(2):194-201
references.pmid: 1546799
references.citation: Anat Embryol (Berl). 1986;175(1):1-6
references.pmid: 3799983
references.citation: Cell. 2007 Sep 21;130(6):1120-33
references.pmid: 17889654
references.citation: Dev Biol. 2005 Apr 15;280(2):396-406
references.pmid: 15882581
references.citation: Annu Rev Cell Dev Biol. 2005;21:247-69
references.pmid: 16212495
references.citation: Hum Mol Genet. 2011 Mar 15;20(6):1143-53
references.pmid: 21212101
references.citation: Dev Cell. 2010 May 18;18(5):698-712
references.pmid: 20493806
references.citation: Mech Dev. 1993 Jan;40(1-2):85-97
references.pmid: 8382938
references.citation: Nat Methods. 2011 Jul 28;8(8):612-3
references.pmid: 21799493
references.citation: Dev Cell. 2010 Apr 20;18(4):579-91
references.pmid: 20412773
references.citation: Dev Dyn. 2012 Jan;241(1):3-15
references.pmid: 22174083
references.citation: EMBO J. 2008 Apr 23;27(8):1231-42
references.pmid: 18369314
references.citation: Mol Cell Biol. 2007 Apr;27(7):2548-61
references.pmid: 17210638
references.citation: Genes Dev. 2006 Mar 1;20(5):571-85
references.pmid: 16510873
references.citation: Curr Biol. 2007 Dec 4;17(23):2054-60
references.pmid: 17980593