title: Tmem88a mediates GATA-dependent specification of cardiomyocyte progenitors by restricting WNT signaling.
abstract: Biphasic control of WNT signaling is essential during cardiogenesis, but how the pathway switches from promoting cardiac mesoderm to restricting cardiomyocyte progenitor fate is unknown. We identified genes expressed in lateral mesoderm that are dysregulated in zebrafish when both gata5 and gata6 are depleted, causing a block to cardiomyocyte specification. This screen identified tmem88a, which is expressed in the early cardiac progenitor field and was previously implicated in WNT modulation by overexpression studies. Depletion of tmem88a results in a profound cardiomyopathy, secondary to impaired cardiomyocyte specification. In tmem88a morphants, activation of the WNT pathway exacerbates the cardiomyocyte deficiency, whereas WNT inhibition rescues progenitor cells and cardiogenesis. We conclude that specification of cardiac fate downstream of gata5/6 involves activation of the tmem88a gene to constrain WNT signaling and expand the number of cardiac progenitors. Tmem88a is a novel component of the regulatory mechanism controlling the second phase of biphasic WNT activity essential for embryonic cardiogenesis.
authors.affiliation: Department of Surgery, Weill Cornell Medical College, Cornell University, 1300 York Ave., LC-708, New York, NY, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Novikov
authors.forename: Todd
authors.initials: T
authors.lastname: Evans
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D009202:Cardiomyopathies / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000378:metabolism; D050980:GATA Transcription Factors / Q000378:metabolism*; D050992:GATA5 Transcription Factor / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D056726:Genetic Association Studies; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D060172:Morpholinos / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D038081:Organogenesis / Q000187:drug effects / Q000235:genetics; D010641:Phenotype; D034443:RNA Transport / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D050980:GATA Transcription Factors; D050992:GATA5 Transcription Factor; C525956:Gata6 protein, zebrafish; D008565:Membrane Proteins; D060172:Morpholinos; D012333:RNA, Messenger; C584121:Tmem88a protein, zebrafish; D029961:Zebrafish Proteins; C494754:gata5 protein, zebrafish
keywords: Cardiac fate; Heart development; Lineage commitment; Zebrafish
references.citation: Dev Biol. 2002 Jan 15;241(2):229-37
references.pmid: 11784107
references.citation: Bioinformatics. 2009 Jul 15;25(14):1754-60
references.pmid: 19451168
references.citation: Dev Biol. 2004 Mar 15;267(2):490-504
references.pmid: 15013808
references.citation: Development. 2007 Feb;134(3):479-89
references.pmid: 17185322
references.citation: Dev Cell. 2008 Dec;15(6):923-34
references.pmid: 19081079
references.citation: Nat Rev Genet. 2001 Jan;2(1):39-48
references.pmid: 11253067
references.citation: Curr Biol. 2003 Dec 16;13(24):2138-47
references.pmid: 14680629
references.citation: Dev Biol. 2011 Apr 1;352(1):154-63
references.pmid: 21238449
references.citation: J Anat. 2010 Jan;216(1):92-107
references.pmid: 20402826
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D581-5
references.pmid: 16381936
references.citation: Dev Cell. 2003 Dec;5(6):877-89
references.pmid: 14667410
references.citation: Mech Dev. 2013 Feb;130(2-3):122-31
references.pmid: 23072875
references.citation: Development. 1995 Oct;121(10):3141-50
references.pmid: 7588049
references.citation: Nat Rev Genet. 2005 Nov;6(11):826-35
references.pmid: 16304598
references.citation: Development. 2011 Oct;138(19):4193-8
references.pmid: 21896629
references.citation: Dev Biol. 2001 Oct 1;238(1):97-109
references.pmid: 11783996
references.citation: Nat Rev Genet. 2002 Jul;3(7):544-56
references.pmid: 12094232
references.citation: Curr Top Dev Biol. 2010;90:1-41
references.pmid: 20691846
references.citation: Development. 2011 Oct;138(19):4199-205
references.pmid: 21896630
references.citation: Nat Protoc. 2009;4(1):44-57
references.pmid: 19131956
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):407-12
references.pmid: 15630097
references.citation: Nature. 2011 May 29;474(7353):645-8
references.pmid: 21623370
references.citation: Cell. 2012 Aug 3;150(3):590-605
references.pmid: 22863011
references.citation: Semin Cell Dev Biol. 2007 Feb;18(1):67-76
references.pmid: 17276708
references.citation: Development. 2008 Nov;135(22):3789-99
references.pmid: 18842815
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19812-7
references.pmid: 17170140
references.citation: J Biol Chem. 2010 Dec 31;285(53):41549-56
references.pmid: 21044957
references.citation: Trends Cardiovasc Med. 2000 Nov;10(8):345-52
references.pmid: 11369261
references.citation: EMBO J. 1991 Dec;10(12):3609-19
references.pmid: 1718739
references.citation: Development. 1998 Mar;125(6):1095-101
references.pmid: 9463356
references.citation: Genes Dev. 1999 Nov 15;13(22):2983-95
references.pmid: 10580005
references.citation: Ann N Y Acad Sci. 2006 Oct;1080:85-96
references.pmid: 17132777
references.citation: Methods Cell Biol. 1999;59:63-85
references.pmid: 9891356
references.citation: Development. 1996 Dec;122(12):3809-16
references.pmid: 9012502
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):10894-9
references.pmid: 17576928
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9685-90
references.pmid: 17522258
references.citation: Dev Biol. 2003 Jun 1;258(1):1-19
references.pmid: 12781678
references.citation: Dev Dyn. 2003 Sep;228(1):30-40
references.pmid: 12950077
references.citation: Dev Cell. 2007 Aug;13(2):254-67
references.pmid: 17681136
references.citation: Genes Dev. 1998 Mar 1;12(5):621-6
references.pmid: 9499398
references.citation: Dev Dyn. 1995 Jul;203(3):253-310
references.pmid: 8589427
references.citation: Curr Opin Genet Dev. 2002 Aug;12(4):416-22
references.pmid: 12100886
references.citation: PLoS One. 2013 Jul 23;8(7):e69666
references.pmid: 23936070
references.citation: Development. 2011 Jun;138(11):2389-98
references.pmid: 21558385
references.citation: J Biol Chem. 2010 Jan 15;285(3):1765-72
references.pmid: 19889636
references.citation: Genome Biol. 2010;11(10):R106
references.pmid: 20979621
references.citation: Cell. 2010 Aug 6;142(3):375-86
references.pmid: 20691899
references.citation: Nature. 2009 Jun 4;459(7247):708-11
references.pmid: 19396158
references.citation: Development. 2001 Aug;128(16):3179-88
references.pmid: 11688566
references.citation: Development. 2011 Aug;138(15):3113-23
references.pmid: 21715426
references.citation: Dev Biol. 2008 May 15;317(2):614-9
references.pmid: 18400219
references.citation: Wiley Interdiscip Rev Syst Biol Med. 2011 Mar-Apr;3(2):191-205
references.pmid: 20830688
references.citation: Curr Top Dev Biol. 2012;100:143-69
references.pmid: 22449843
references.citation: Development. 2003 Jul;130(13):3027-38
references.pmid: 12756184
references.citation: Nucleic Acids Res. 2009 Jan;37(1):1-13
references.pmid: 19033363
references.citation: Circ Res. 2004 Aug 6;95(3):261-8
references.pmid: 15217909
references.citation: Development. 2004 Jul;131(13):3081-91
references.pmid: 15175246
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D768-72
references.pmid: 17991680
references.citation: J Vis Exp. 2009 Mar 25;(25):
references.pmid: 19322135
references.citation: PLoS One. 2010 Jun 15;5(6):e11134
references.pmid: 20559569
references.citation: Development. 1996 Jan;122(1):271-80
references.pmid: 8565839
references.citation: Dev Cell. 2004 May;6(5):685-98
references.pmid: 15130493
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: J Vis Exp. 2012 Jan 10;(59):e3510
references.pmid: 22258109
references.citation: Dev Biol. 2007 Dec 15;312(2):613-22
references.pmid: 17950269
references.citation: Circ Res. 2010 Dec 10;107(12):1428-44
references.pmid: 21148449
references.citation: Development. 1992 Dec;116(4):1021-32
references.pmid: 1295726
references.citation: Dev Cell. 2012 Jul 17;23(1):58-70
references.pmid: 22771034
references.citation: Dev Cell. 2007 Jul;13(1):10-3
references.pmid: 17609106
references.citation: Development. 2008 Oct;135(19):3185-90
references.pmid: 18715946
references.citation: Dev Biol. 2008 Nov 15;323(2):177-88
references.pmid: 18804460
references.citation: Curr Biol. 2005 Mar 29;15(6):489-500
references.pmid: 15797017
references.citation: Dev Dyn. 2000 Apr;217(4):327-42
references.pmid: 10767078
references.citation: Dev Cell. 2001 Sep;1(3):435-40
references.pmid: 11702954