Abstract
The zinc finger transcription factor GATA4 has been implicated in heart development based on its early expression in precardiogenic splanchnic mesoderm and its ability to activate the expression of a number of cardiac-specific genes. To determine the role of GATA4 in embryogenesis, we generated mice homozygous for a GATA4 null allele. Homozygous GATA4 null mice arrested in development between E7.0 and E9.5 because of severe developmental abnormalities. Mutant embryos most notably lacked a primitive heart tube and foregut and developed partially outside the yolk sac. In the mutants, the two bilaterally symmetric promyocardial primordia failed to migrate ventrally but instead remained lateral and generated two independent heart tubes that contained differentiated cardiomyocytes. We show that these deformities resulted from a general loss in lateral to ventral folding throughout the embryo. GATA4 is most highly expressed within the precardiogenic splanchnic mesoderm at the posterior lip of the anterior intestinal portal, corresponding to the region of the embryo that undergoes ventral fusion. We propose that GATA4 is required for the migration or folding morphogenesis of the precardiogenic splanchnic mesodermal cells at the level of the AIP.
References
61
Referenced
945
10.1242/dev.119.4.1301
/ Development / The formation and maintenance of the definitive endoderm lineage in the mouse: Involvement of HNF-3/fork head proteins. (1993){'key': '2021111418441655000_11.8.1061.2', 'first-page': '2235', 'article-title': 'Mouse GATA-4: A retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Mouse GATA-4: A retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart. (1993)10.1006/dbio.1994.1018
{'key': '2021111418441655000_11.8.1061.4', 'first-page': '324', 'article-title': 'Polyvinyl alcohol enhances detection of low abundance transcripts in early stage quail embryos in a nonradioactive whole mount in situ hybridization technique.', 'volume': '17', 'year': '1994', 'journal-title': 'BioTechniques'}
/ BioTechniques / Polyvinyl alcohol enhances detection of low abundance transcripts in early stage quail embryos in a nonradioactive whole mount in situ hybridization technique. (1994)10.1128/MCB.15.2.626
/ Mol. Cell. Biol. / Rescue of GATA-1-deficient embryonic stem cells by heterologous GATA-binding proteins. (1995)10.1242/dev.116.4.1123
/ Development / Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentiatlly expressed during mesodermal patterning in mouse embryos. (1992)10.1242/dev.123.1.293
/ Development / Mutations affecting the cardiovascular system and other internal organs in zebrafish. (1996)10.1101/gad.8.20.2466
10.1016/S0168-9525(00)89008-3
10.1016/S0014-4827(63)80016-6
10.1007/BF00174084
{'key': '2021111418441655000_11.8.1061.12', 'first-page': '1279', 'article-title': 'Human transcription factor GATA-2.', 'volume': '267', 'year': '1992', 'journal-title': 'J. Biol. Chem.'}
/ J. Biol. Chem. / Human transcription factor GATA-2. (1992)10.1073/pnas.91.16.7598
10.1242/dev.124.2.279
/ Development / Murine gastrulation requires HNF-4 regulated gene expression in the visceral endoderm: Tetraploid rescue of HNF-4 -/- embryos. (1997)10.1016/0092-8674(89)90940-9
{'key': '2021111418441655000_11.8.1061.16', 'first-page': '63', 'article-title': 'Origin and differentiation of extra-embryonic tissues in the mouse.', 'volume': '24', 'year': '1983', 'journal-title': 'Int. Rev. Exp. Pathol.'}
/ Int. Rev. Exp. Pathol. / Origin and differentiation of extra-embryonic tissues in the mouse. (1983)10.1002/jez.1401100105
10.1093/emboj/16.2.355
{'key': '2021111418441655000_11.8.1061.19', 'first-page': '3115', 'article-title': 'A hormone-encoding gene identifies a pathway for cardiac but not skeletal muscle gene transcription.', 'volume': '14', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / A hormone-encoding gene identifies a pathway for cardiac but not skeletal muscle gene transcription. (1994)10.1128/MCB.15.8.4095
/ Mol. Cell. Biol. / Inhibition of transcription factor GATA-4 expression blocks in vitro cardiac muscle differentiation. (1995)10.1073/pnas.92.3.850
10.1006/dbio.1994.1206
{'key': '2021111418441655000_11.8.1061.23', 'first-page': '7517', 'article-title': 'The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells.', 'volume': '14', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells. (1994){'key': '2021111418441655000_11.8.1061.24', 'first-page': '257', 'article-title': 'The Xenopus GATA-4/5/6 genes are associated with cardiac specification and can regulate cardiac-specific transcription during embryogenesis.', 'volume': '174', 'year': '1996', 'journal-title': 'Dev. Biol.'}
/ Dev. Biol. / The Xenopus GATA-4/5/6 genes are associated with cardiac specification and can regulate cardiac-specific transcription during embryogenesis. (1996)- Kaufman, M.H. 1992. The atlas of mouse development (ed. M.H. Kaufman), pp. 2–5. Academic Press, San Diego, CA.
10.1242/dev.118.3.817
/ Development / GATA-4 is a novel transcription factor expressed in endocardium of the developing heart. (1993)-
Ko, J.L. and J.D. Engel. 1993. DNA-binding specificies of the GATA transcription factor family. Mol. Cell. Biol. 13: 4011–4022.
(
10.1128/MCB.13.7.4011
) 10.1016/S0021-9258(17)31636-8
/ J. Biol Chem. / GATA 4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut. (1994)10.1016/S0021-9258(18)98533-9
/ J. Biol. Chem. / Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells. (1991)10.1101/gad.9.13.1654
10.1101/gad.4.11.1886
10.1038/344444a0
10.1038/360313a0
{'key': '2021111418441655000_11.8.1061.34', 'first-page': '3999', 'article-title': 'DNA-binding specificity of the GATA family transcription factors.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / DNA-binding specificity of the GATA family transcription factors. (1993){'key': '2021111418441655000_11.8.1061.35', 'first-page': '4947', 'article-title': 'GATA-4 positively regulates expression of the α-cardiac myosin heavy chain gene in vivo.', 'volume': '14', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / GATA-4 positively regulates expression of the α-cardiac myosin heavy chain gene in vivo. (1994)10.1006/dbio.1996.0165
10.1006/dbio.1996.8485
10.1016/S1050-1738(96)00086-2
10.1126/science.272.5262.671
10.1073/pnas.90.5.1676
10.1182/blood.V80.3.575.575
/ Blood / GATA-binding transcription factors in hematopoietic cells. (1992)10.1038/ng0995-40
10.1038/349257a0
10.1016/0076-6879(93)25054-6
10.1016/0925-4773(93)90060-B
10.1242/dev.118.1.47
/ Development / Differential expression of multiple fork head related genes during gastrulation and axial pattern formation in the mouse embryo. (1993)10.1002/j.1460-2075.1993.tb05935.x
/ EMBO J. / A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo. (1993)10.1242/dev.121.11.3877
/ Development / Targeted mutagenesis of the transcription factor GATA-4 gene in mouse embryonic stem cells disrupts visceral endoderm differentiation in vitro. (1995)10.1126/science.270.5244.1995
10.1242/dev.123.1.285
/ Development / Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo. (1996)10.1016/0012-1606(68)90043-2
10.1002/aja.1002040305
/ Dev. Dynam. / Relationship between fibronection expression during gastrulation and heart formation in the rat embryo. (1995){'key': '2021111418441655000_11.8.1061.53', 'first-page': '17772', 'article-title': 'Regulation of rat brain natriuretic peptide transcription.', 'volume': '269', 'year': '1994', 'journal-title': 'J. Biol. Chem.'}
/ J. Biol. Chem. / Regulation of rat brain natriuretic peptide transcription. (1994)10.1038/384474a0
10.1038/371221a0
10.1038/339446a0
10.1128/MCB.15.2.634
/ Mol. Cell. Biol. / The C-terminal zinc finger of GATA-1 or GATA-2 is sufficient to induce megakaryocyte differentiation of an early myeloid cell line. (1995)10.1128/MCB.10.9.4854
10.1101/gad.4.10.1650
{'key': '2021111418441655000_11.8.1061.60', 'first-page': '4562', 'article-title': 'Distinct roles for the two cGATA-1 finger domains.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Distinct roles for the two cGATA-1 finger domains. (1992)10.1016/S0021-9258(18)54446-X
/ J. Biol. Chem. / GATA-binding transcription factors in mast cells regulate the mast cell carboxypeptidase A gene. (1991)
Dates
Type | When |
---|---|
Created | 18 years, 2 months ago (June 5, 2007, 5:15 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 14, 2021, 10:01 p.m.) |
Indexed | 3 weeks, 3 days ago (Aug. 6, 2025, 8:28 a.m.) |
Issued | 28 years, 4 months ago (April 15, 1997) |
Published | 28 years, 4 months ago (April 15, 1997) |
Published Online | 28 years, 4 months ago (April 15, 1997) |
Published Print | 28 years, 4 months ago (April 15, 1997) |
@article{Molkentin_1997, title={Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis.}, volume={11}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.11.8.1061}, DOI={10.1101/gad.11.8.1061}, number={8}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Molkentin, J D and Lin, Q and Duncan, S A and Olson, E N}, year={1997}, month=apr, pages={1061–1072} }