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PMID:18400219

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Citation

Zhao, R, Watt, AJ, Battle, MA, Li, J, Bondow, BJ and Duncan, SA (2008) Loss of both GATA4 and GATA6 blocks cardiac myocyte differentiation and results in acardia in mice. Dev. Biol. 317:614-9

Abstract

Despite significant advances in identifying signaling molecules that induce cardiogenesis in mammals, the transcription factors that control the onset of cardiac myocyte gene expression have remained elusive. Candidates include the zinc finger transcription factors GATA binding proteins 4 and 6 (GATA4, GATA6). The individual loss of either protein in mice results in lethality prior to the onset of heart development due to defects in the extra-embryonic endoderm; however, when this extra-embryonic deficiency is circumvented using tetraploid embryo complementation, cardiac myocyte differentiation initiates normally. Here we show that these factors have redundant roles in controlling the onset of cardiac myocyte differentiation. As a consequence, Gata4(-/-)Gata6(-/-) embryos completely lack hearts, although second heart field progenitor cells are still generated. Our data support a model whereby GATA4 or GATA6 are essential for expression of the network of transcription factors that regulate the onset of cardiac myocyte gene expression during mammalian development.

Links

PubMed PMC2423416 Online version:10.1016/j.ydbio.2008.03.013

Keywords

Animals; Cell Differentiation/physiology; Endoderm/physiology; GATA4 Transcription Factor/deficiency; GATA4 Transcription Factor/metabolism; GATA6 Transcription Factor/deficiency; GATA6 Transcription Factor/metabolism; Gene Expression Regulation, Developmental/genetics; Heart/embryology; Immunohistochemistry; In Situ Hybridization; Mice; Mice, Knockout; Models, Biological; Myocytes, Cardiac/cytology; Myocytes, Cardiac/metabolism; Oligonucleotides; Reverse Transcriptase Polymerase Chain Reaction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:GATA4

acts_upstream_of_or_within

GO:0010468: regulation of gene expression

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:107516

P

  • occurs_in:(CL:0002322)
  • has_input:(MGI:MGI:97350)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:1888496)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:102541)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:99458)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:109497)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:103577)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:103580)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:107785)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:1096325)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:101791)

Seeded From UniProt

complete

MOUSE:GATA4

acts_upstream_of_or_within

GO:0035239: tube morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:107516

P

Seeded From UniProt

complete

MOUSE:GATA6

acts_upstream_of_or_within

GO:0010468: regulation of gene expression

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95664

P

  • occurs_in:(CL:0002322)
  • has_input:(MGI:MGI:97350)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:1888496)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:102541)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:99458)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:109497)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:103577)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:103580)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:107785)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:1096325)|occurs_in(CL:0002322)
  • has_input:(MGI:MGI:101791)

Seeded From UniProt

complete

MOUSE:GATA6

acts_upstream_of_or_within

GO:0055007: cardiac muscle cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3793425

P

  • results_in_acquisition_of_features_of:(CL:0000352)

Seeded From UniProt

complete

MOUSE:GATA6

acts_upstream_of_or_within

GO:0055007: cardiac muscle cell differentiation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95664

P

  • results_in_acquisition_of_features_of:(CL:0000352)

Seeded From UniProt

complete

MOUSE:GATA6

acts_upstream_of_or_within

GO:0055007: cardiac muscle cell differentiation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95664

P

  • results_in_acquisition_of_features_of:(CL:0000187)

Seeded From UniProt

complete

MOUSE:GATA6

acts_upstream_of_or_within

GO:0035239: tube morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95664

P

Seeded From UniProt

complete

MOUSE:GATA4

acts_upstream_of_or_within

GO:0035239: tube morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:107516

P

has_participant:(EMAPA:16105)

Seeded From UniProt

complete

MOUSE:GATA4

acts_upstream_of_or_within

GO:0010468: regulation of gene expression

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:107516

P

  • occurs_in:(CL:0002322)
  • has_regulation_target:(MGI:MGI:97350)|occurs_in(CL:0002322)
  • has_regulation_target:(MGI:MGI:1888496)|occurs_in(CL:0002322)
  • has_regulation_target:(MGI:MGI:102541)|occurs_in(CL:0002322)
  • has_regulation_target:(MGI:MGI:99458)|occurs_in(CL:0002322)
  • has_regulation_target:(MGI:MGI:109497)|occurs_in(CL:0002322)
  • has_regulation_target:(MGI:MGI:103577)|occurs_in(CL:0002322)
  • has_regulation_target:(MGI:MGI:103580)|occurs_in(CL:0002322)
  • has_regulation_target:(MGI:MGI:107785)|occurs_in(CL:0002322)
  • has_regulation_target:(MGI:MGI:1096325)|occurs_in(CL:0002322)
  • has_regulation_target:(MGI:MGI:101791)

Seeded From UniProt

complete

MOUSE:GATA4

acts_upstream_of_or_within

GO:0055007: cardiac muscle cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3793424

P

Seeded From UniProt

complete

MOUSE:GATA4

acts_upstream_of_or_within

GO:0055007: cardiac muscle cell differentiation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:107516

P

Seeded From UniProt

complete


See also

References

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