title: CASZ1 promotes vascular assembly and morphogenesis through the direct regulation of an EGFL7/RhoA-mediated pathway.
abstract: The formation of the vascular system is essential for embryonic development and homeostasis. However, transcriptional control of this process is not fully understood. Here we report an evolutionarily conserved role for the transcription factor CASZ1 (CASTOR) in blood vessel assembly and morphogenesis. In the absence of CASZ1, Xenopus embryos fail to develop a branched and lumenized vascular system, and CASZ1-depleted human endothelial cells display dramatic alterations in adhesion, morphology, and sprouting. Mechanistically, we show that CASZ1 directly regulates Epidermal Growth Factor-Like Domain 7 (Egfl7). We further demonstrate that defects of CASZ1- or EGFL7-depleted cells are in part due to diminished RhoA expression and impaired focal adhesion localization. Moreover, these abnormal endothelial cell behaviors in CASZ1-depleted cells can be rescued by restoration of Egfl7. Collectively, these studies show that CASZ1 is required to directly regulate an EGFL7/RhoA-mediated pathway to promote vertebrate vascular development.
authors: McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA.
authors: Marta S
authors: MS
authors: Charpentier
authors: Kathleen S
authors: KS
authors: Christine
authors: Nirav M
authors: NM
authors: Amin
authors: Kerry M
authors: KM
authors: Dorr
authors: Erich J
authors: EJ
authors: Kushner
authors: Victoria L
authors: VL
authors: Bautch
authors: Joan M
authors: JM
authors: Taylor
authors: Frank L
authors: FL
authors: Conlon
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D066255:EGF Family of Proteins; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism*; D047108:Embryonic Development; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000254:growth & development / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C511127:CASZ1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D066255:EGF Family of Proteins; C527877:EGFL7 protein, human; C586713:Egfl7 protein, Xenopus; D016228:Endothelial Growth Factors; D016326:Extracellular Matrix Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D020742:rhoA GTP-Binding Protein
references: Dev Cell. 2008 Apr;14(4):616-23
references: 18410736
references: Dev Cell. 2009 Oct;17(4):505-15
references: 19853564
references: Dev Dyn. 1997 Sep;210(1):66-77
references: 9286596
references: Development. 2010 Jun;137(11):1919-29
references: 20460370
references: Nature. 2011 May 19;473(7347):298-307
references: 21593862
references: Cell. 1995 Apr 7;81(1):53-62
references: 7536630
references: Cell. 2004 Jan 23;116(2):167-79
references: 14744429
references: Microvasc Res. 2003 Sep;66(2):102-12
references: 12935768
references: Am J Pathol. 2005 Jul;167(1):275-84
references: 15972971
references: Methods. 2002 Jan;26(1):37-47
references: 12054903
references: Nat Med. 2003 Jun;9(6):653-60
references: 12778163
references: Circulation. 2010 Jun 1;121(21):2302-9
references: 20479155
references: Dev Cell. 2009 Feb;16(2):180-95
references: 19217421
references: J Angiogenes Res. 2010 Jun 08;2(1):9
references: 20529320
references: J Mol Cell Cardiol. 2010 Mar;48(3):433-9
references: 19837080
references: Genes Dev. 2006 May 1;20(9):1187-202
references: 16651659
references: Gene Expr Patterns. 2006 Aug;6(6):613-9
references: 16431163
references: Methods Cell Biol. 1991;36:685-95
references: 1811161
references: Cell. 2011 Sep 16;146(6):873-87
references: 21925313
references: Nat Cell Biol. 2009 Jul;11(7):873-80
references: 19503073
references: J Cell Biol. 1996 Jun;133(6):1403-15
references: 8682874
references: Dev Dyn. 2005 Aug;233(4):1546-53
references: 15965984
references: Blood. 2010 Dec 23;116(26):6133-43
references: 20947685
references: Blood. 2012 Feb 23;119(8):1946-55
references: 22096252
references: Nat Genet. 2009 Jun;41(6):677-87
references: 19430479
references: Birth Defects Res C Embryo Today. 2007 Dec;81(4):270-85
references: 18228260
references: J Neurooncol. 2000 Oct-Nov;50(1-2):1-15
references: 11245270
references: Development. 2008 Jun;135(11):1903-11
references: 18469221
references: Dev Dyn. 2004 Jun;230(2):316-24
references: 15162510
references: Nat Cell Biol. 2010 May;12(5):457-67
references: 20383141
references: Mech Dev. 1996 Oct;59(2):129-40
references: 8951791
references: Dev Dyn. 2006 Jun;235(6):1623-30
references: 16477648
references: J Cell Sci. 2002 Mar 15;115(Pt 6):1123-36
references: 11884513
references: Immunity. 1998 Oct;9(4):555-63
references: 9806641
references: Dev Cell. 2008 Aug;15(2):261-71
references: 18694565
references: Nat Rev Mol Cell Biol. 2010 Sep;11(9):633-43
references: 20729930
references: Genes Dev. 2002 Oct 1;16(19):2530-43
references: 12368264
references: Dev Biol. 2003 Feb 1;254(1):50-67
references: 12606281
references: J R Soc Interface. 2011 Mar 6;8(56):305-11
references: 20826475
references: Int J Biochem Cell Biol. 2001 Apr;33(4):391-407
references: 11312108
references: Dev Dyn. 1999 Dec;216(4-5):420-33
references: 10633861
references: Development. 2008 Dec;135(24):3989-93
references: 18987025
references: Arterioscler Thromb Vasc Biol. 2011 Jul;31(7):1469-75
references: 21677289
references: Dev Cell. 2011 Apr 19;20(4):526-39
references: 21396893
references: Dev Cell. 2008 Aug;15(2):272-84
references: 18694566
references: EMBO J. 2008 Jun 18;27(12):1658-70
references: 18497746
references: Dev Biol. 2006 Aug 1;296(1):177-89
references: 16750822
references: RNA. 2010 Mar;16(3):495-505
references: 20075166
references: Circ Res. 2009 May 22;104(10):1151-9
references: 19407242
references: Nature. 2004 Apr 15;428(6984):754-8
references: 15085134
references: Methods Enzymol. 2000;325:273-84
references: 11036610