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18 results on '"Morrisey, E. E."'

1. Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm

Author

Hogan, B. L. M., Taranova, O., Okubo, T., Morrisey, E. E., Nam, K.-T., Goldenring, J. R., Kurotani, R., Que, J., and Pevny, L. H.

Subjects
stomatognathic system, embryonic structures, respiratory system
Abstract

Sox2 is expressed in developing foregut endoderm, with highest levels in the future esophagus and anterior stomach. By contrast, Nkx2.1 (Titf1) is expressed ventrally, in the future trachea. In humans, heterozygosity for SOX2 is associated with anopthalmiaesophageal-genital syndrome (OMIM 600992), a condition including esophageal atresia (EA) and tracheoesophageal fistula (TEF), in which the trachea and esophagus fail to separate. Mouse embryos heterozygous for the null allele, Sox2EGFP, appear normal. However, further reductions in Sox2, using Sox2LP and Sox2COND hypomorphic alleles, result in multiple abnormalities. Approximately 60% of Sox2EGFP/COND embryos have EA with distal TEF in which Sox2 is undetectable by immunohistochemistry or western blot. The mutant esophagus morphologically resembles the trachea, with ectopic expression of Nkx2.1, a columnar, ciliated epithelium, and very few p63+ basal cells. By contrast, the abnormal foregut of Nkx2.1-null embryos expresses elevated Sox2 and p63, suggesting reciprocal regulation of Sox2 and Nkx2.1 during early dorsal/ventral foregut patterning. Organ culture experiments further suggest that FGF signaling from the ventral mesenchyme regulates Sox2 expression in the endoderm. In the 40% Sox2EGFP/COND embryos in which Sox2 levels are ~18% of wild type there is no TEF. However, the esophagus is still abnormal, with luminal mucus-producing cells, fewer p63+ cells, and ectopic expression of genes normally expressed in glandular stomach and intestine. In all hypomorphic embryos the forestomach has an abnormal phenotype, with reduced keratinization, ectopic mucus cells and columnar epithelium. These findings suggest that Sox2 plays a second role in establishing the boundary between the keratinized, squamous esophagus/forestomach and glandular hindstomach.

Published
2007
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6. GATA-6 activates transcription of surfactant protein A.

Author

Bruno, M D, Korfhagen, T R, Liu, C, Morrisey, E E, and Whitsett, J A

Abstract

Surfactant protein A (SP-A) is a member of the collectin family of innate host defense molecules expressed primarily in respiratory epithelial cells of the lung. SP-A concentrations are influenced by both cell-specific and ubiquitous nuclear proteins that regulate SP-A gene transcription in a cell-selective and temporally regulated manner. In this work, a consensus GATA-binding site (GBS) was identified at positions -69 to -64 of the mouse SP-A gene. The transcriptional activity of wild-type SP-A reporter constructs in HeLa cells was increased 5-10-fold when cotransfected with a GATA-6 expression plasmid. Deletion of the GBS completely blocked transactivation by GATA-6. Transfection of a construct expressing GATA-6-engrailed fusion protein inhibited basal expression of the SP-A/chloramphenicol acetyltransferase construct in MLE-15 cells. Nuclear extract proteins from MLE-15 cells bound to the GBS in the mouse SP-A gene, and a supershifted band was detected with a GATA-6-specific antibody. Transactivation of the wild-type SP-A constructs by GATA-6 increased transcriptional activity 7-10-fold, whereas thyroid transcription factor-1 (TTF-1) increased the activity of these constructs 12-18-fold. The effects of cotransactivating with both GATA-6 and TTF-1 expression constructs were additive. However, mutation of the TTF-1-binding sites alone or in combination decreased GATA-6 transactivation. Likewise, mutation of the GBS blocked TTF-1 activation of the SP-A promoter. In situ hybridization demonstrated GATA-6 mRNA in the peripheral epithelial cells of fetal mouse lung, consistent with the sites of SP-A expression. GATA-6 is expressed in respiratory epithelial cells and binds to a cis-acting element in the SP-A gene promoter, activating the transcriptional activity of the gene.

Published
2000

7. GATA-4 activates transcription via two novel domains that are conserved within the GATA-4/5/6 subfamily.

Author

Morrisey, E E, Ip, H S, Tang, Z, and Parmacek, M S

Abstract

GATA-4 is one of the earliest developmental markers of the precardiac mesoderm, heart, and gut and has been shown to activate regulatory elements controlling transcription of genes encoding cardiac-specific proteins. To elucidate the molecular mechanisms underlying the transcriptional activity of the GATA-4 protein, structure-function analyses were performed. These analyses revealed that the C-terminal zinc finger and adjacent basic domain of GATA-4 is bifunctional, modulating both DNA-binding and nuclear localization activities. The N terminus of the protein encodes two independent transcriptional Activation Domains (amino acids 1-74 and amino acids 130-177). Amino acid residues were identified within each domain that are required for transcriptional activation. Finally, we have shown that regions of Xenopus GATA-5 and -6 corresponding to Activation Domains I and II, respectively, function as potent transcriptional activators. The identification and functional characterization of two evolutionarily conserved transcriptional Activation Domains within the GATA-4/5/6 subfamily suggests that each of these domains modulates critical functions in the transcriptional regulatory program(s) encoded by GATA-4, -5, and -6 during vertebrate development. As such these data provide novel insights into the molecular mechanisms that control development of the heart.

Published
1997

8. GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo.

Author

Morrisey, E E, Tang, Z, Sigrist, K, Lu, M M, Jiang, F, Ip, H S, and Parmacek, M S

Abstract

GATA6 belongs to a family of zinc finger transcription factors that play important roles in transducing nuclear events that regulate cellular differentiation and embryonic morphogenesis in vertebrate species. To examine the function of GATA6 during embryonic development, gene targeting was used to generate GATA6-deficient (GATA6(-/-)) ES cells and mice harboring a null mutation in GATA6. Differentiated embryoid bodies derived from GATA6(-/-) ES cells lack a covering layer of visceral endoderm and severely attenuate, or fail to express, genes encoding early and late endodermal markers, including HNF4, GATA4, alpha-fetoprotein (AFP), and HNF3beta. Homozygous GATA6(-/-) mice died between embryonic day (E) 6.5 and E7. 5 and exhibited a specific defect in endoderm differentiation including severely down-regulated expression of GATA4 and absence of HNF4 gene expression. Moreover, widespread programmed cell death was observed within the embryonic ectoderm of GATA6-deficient embryos, a finding also observed in HNF4-deficient embryos. Consistent with these data, forced expression of GATA6 activated the HNF4 promoter in nonendodermal cells. Finally, to examine the function of GATA6 during later embryonic development, GATA6(-/-)-C57BL/6 chimeric mice were generated. lacZ-tagged GATA6(-/-) ES cells contributed to all embryonic tissues with the exception of the endodermally derived bronchial epithelium. Taken together, these data suggest a model in which GATA6 lies upstream of HNF4 in a transcriptional cascade that regulates differentiation of the visceral endoderm. In addition, these data demonstrate that GATA6 is required for establishment of the endodermally derived bronchial epithelium.

Published
1998

9. Developmental pattern of expression and genomic organization of the calponin-h1 gene. A contractile smooth muscle cell marker.

Author

Samaha, F F, Ip, H S, Morrisey, E E, Seltzer, J, Tang, Z, Solway, J, and Parmacek, M S

Abstract

Calponin-h1 is a 34-kDa myofibrillar thin filament, actin-binding protein that is expressed exclusively in smooth muscle cells (SMCs) in adult animals. To examine the molecular mechanisms that regulate SMC-specific gene expression, we have examined the temporal, spatial, and cell cycle-regulated patterns of expression of calponin-h1 gene expression and isolated and structurally characterized the murine calponin-h1 gene. Calponin-h1 mRNA is expressed exclusively in SMC-containing tissues in adult animals. During murine embryonic development, calponin-h1 gene expression is (i) detectable in E9.5 embryos in the dorsal aorta, cardiac outflow tract, and tubular heart, (ii) sequentially up-regulated in SMC-containing tissues, and (iii) down-regulated to non-detectable levels in the heart during late fetal development. In addition, the gene is expressed in resting rat aortic SMCs, but its expression is rapidly down-regulated when growth-arrested cells reenter phase G1 of the cell cycle and proliferate. Calponin-h1 is encoded by a 10.7-kilobase single copy gene composed of seven exons, which is part of a multigene family. Transient transfection analyses demonstrated that 1.5 kilobases of calponin-h1 5'-flanking sequence is sufficient to program high level transcription of a luciferase reporter gene in cultured primary rat aortic SMCs and the smooth muscle cell line, A7r5. Taken together, these data suggest that the calponin-h1 gene will serve as an excellent model system with which to examine the molecular mechanisms that regulate SMC lineage specification, differentiation, and phenotypic modulation.

Published
1996

10. Structure and expression of a smooth muscle cell-specific gene, SM22 alpha.

Author

Solway, J, Seltzer, J, Samaha, F F, Kim, S, Alger, L E, Niu, Q, Morrisey, E E, Ip, H S, and Parmacek, M S

Abstract

SM22 alpha is expressed exclusively in smooth muscle-containing tissues of adult animals and is one of the earliest markers of differentiated smooth muscle cells (SMCs). To examine the molecular mechanisms that regulate SMC-specific gene expression, we have isolated and structurally characterized the murine SM22 alpha gene. SM22 alpha is a 6.2-kilobase single copy gene composed of five exons. SM22 alpha mRNA is expressed at high levels in the aorta, uterus, lung, and intestine, and in primary cultures of rat aortic SMCs, and the SMC line, A7r5. In contrast to genes encoding SMC contractile proteins, SM22 alpha gene expression is not decreased in proliferating SMCs. Transient transfection experiments demonstrated that 441 base pairs of SM22 alpha 5'-flanking sequence was necessary and sufficient to program high level transcription of a luciferase reporter gene in both primary rat aortic SMCs and A7r5 cells. DNA sequence analyses revealed that the 441-base pair promoter contains two CArG/SRF boxes, a CACC box, and one potential MEF-2 binding site, cis-acting elements which are each important regulators of striated muscle transcription. Taken together, these studies have identified the murine SM22 alpha promoter as an excellent model system for studies of developmentally regulated, lineage-specific gene expression in SMCs.

Published
1995

11. Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta- catenin signaling pathways in hair follicle induction

Author

Zhang, Y., Tomann, P., Andl, T., Gallant, NM., Huelsken, J., Jerchow, B., Birchmeier, W., Paus, R., Piccolo, S., Mikkola, M. L., Morrisey, E. E., Overbeek, P. A., Scheidereit, C., Millar, S. E., and Schmidt-Ullrich, R.

Subjects
integumentary system
Abstract

Wnt/beta-catenin and NF-kappaB signaling mechanisms provide central controls in development and disease, but how these pathways intersect is unclear. Using hair follicle induction as a model system, we show that patterning of dermal Wnt/beta-catenin signaling requires epithelial beta- catenin activity. We find that Wnt/beta-catenin signaling is absolutely required for NF-kappaB activation, and that Edar is a direct Wnt target gene. Wnt/beta-catenin signaling is initially activated independently of EDA/EDAR/NF-kappaB activity in primary hair follicle primordia. However, Eda/Edar/NF-kappaB signaling is required to refine the pattern of Wnt/beta-catenin activity, and to maintain this activity at later stages of placode development. We show that maintenance of localized expression of Wnt10b and Wnt10a requires NF-kappaB signaling, providing a molecular explanation for the latter observation, and identify Wnt10b as a direct NF-kappaB target. These data reveal a complex interplay and interdependence of Wnt/beta-catenin and EDA/EDAR/NF-kappaB signaling pathways in initiation and maintenance of primary hair follicle placodes.

12. beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis

Author

Mucenski, M. L., Wert, S. E., Nation, J. M., Loudy, D. E., Huelsken, J., Birchmeier, W., Morrisey, E. E., and Whitsett, J. A.

Subjects
respiratory system, respiratory tract diseases
Abstract

The lungs are divided, both structurally and functionally, into two distinct components, the proximal airways, which conduct air, and the peripheral airways, which mediate gas exchange. The mechanisms that control the specification of these two structures during lung development are currently unknown. Here we show that beta-catenin signaling is required for the formation of the distal, but not the proximal, airways. When the gene for beta-catenin was conditionally excised in epithelial cells of the developing mouse lung prior to embryonic day 14.5, the proximal lung tubules grew and differentiated appropriately. The mice, however, died at birth because of respiratory failure. Analysis of the lungs by in situ hybridization and immunohistochemistry, using molecular markers of the epithelial and mesenchymal components of both proximal and peripheral airways, showed that the lungs were composed primarily of proximal airways. These observations establish, for the first time, both the sites and timing of specification of the proximal and peripheral airways in the developing lung, and that beta-catenin is one of the essential components of this specification.

13. The bone morphogenic protein antagonist gremlin regulates proximal-distal patterning of the lung.

Author

Lu MM, Yang H, Zhang L, Shu W, Blair DG, and Morrisey EE

Subjects
Animals, Cytokines, Embryo, Mammalian metabolism, Embryo, Mammalian physiology, Embryonic and Fetal Development, Humans, Mice embryology, Mice, Transgenic genetics, Muscle, Smooth embryology, Proteins genetics, Proteins metabolism, Proteolipids genetics, Pulmonary Surfactants genetics, Pulmonary Surfactants metabolism, Transcription, Genetic physiology, Body Patterning physiology, Bone Morphogenetic Proteins antagonists & inhibitors, Intercellular Signaling Peptides and Proteins, Lung embryology, Proteins physiology
Abstract

The proximal-distal patterning of lung epithelium involves a complex series of signaling and transcriptional events resulting in the programmed differentiation of highly specialized cells for gas exchange and surfactant protein expression essential for postnatal lung function. The BMP signaling pathway has been shown to regulate cellular differentiation in the lung as well as other tissues. In this report, we show that the can family of related BMP antagonists, including gremlin, cer-1, PRDC, and Dan are expressed in the lung during embryonic development with gremlin expression observed in the proximal airway epithelium. The role of gremlin in lung development was explored by overexpressing it in the distal lung epithelium of transgenic mice using the human SP-C promoter. SP-C/gremlin transgenic mice exhibited a disruption of the proximal-distal patterning found in the airways of the mammalian lung. Expanded expression of the proximal epithelial cell markers CC10 and HFH-4 (Foxj1) was observed in the distal regions of transgenic lungs. Furthermore, smooth muscle alpha-actin expression was observed surrounding the distal airways of SP-C/gremlin mice, indicating a proximalization of distal lung tubules. These data suggest that gremlin plays an important role in lung morphogenesis by regulating the proximal-distal patterning of the lung during development., (Copyright 2001 Wiley-Liss, Inc.)

Published
2001
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14. Characterization of a new subfamily of winged-helix/forkhead (Fox) genes that are expressed in the lung and act as transcriptional repressors.

Author

Shu W, Yang H, Zhang L, Lu MM, and Morrisey EE

Subjects
Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, DNA, Complementary, Epithelium metabolism, Forkhead Transcription Factors, Lung embryology, Mice, Molecular Sequence Data, Repressor Proteins chemistry, Repressor Proteins pharmacology, Sequence Homology, Amino Acid, Gene Expression Regulation, Developmental, Lung metabolism, Repressor Proteins genetics, Repressor Proteins physiology, Transcription Factors
Abstract

Epithelial gene expression in the lung is thought to be regulated by the coordinate activity of several different families of transcription factors including the Fox family of winged-helix/forkhead DNA-binding proteins. In this report, we have identified and characterized two members of this Fox gene family, Foxp1 and Foxp2, and show that they comprise a new subfamily of Fox genes expressed in the lung. Foxp1 and Foxp2 are expressed at high levels in the lung as early as E12.5 of mouse development with Foxp2 expression restricted to the airway epithelium. In addition, Foxp1 and Foxp2 are expressed at lower levels in neural, intestinal, and cardiovascular tissues during development. Upon differentiation of the airway epithelium along the proximal-distal axis, Foxp2 expression becomes restricted to the distal alveolar epithelium whereas Foxp1 expression is observed in the distal epithelium and mesenchyme. Foxp1 and Foxp2 can regulate epithelial lung gene transcription as was demonstrated by their ability to dramatically repress the mouse CC10 promoter and, to a lesser extent, the human surfactant protein C promoter. In addition, GAL4 fusion proteins encoding subdomains of Foxp1 and Foxp2 demonstrate that an independent and homologous transcriptional repression domain lies within the N-terminal end of the proteins. Together, these studies suggest that Foxp1 and Foxp2 are important regulators of lung epithelial gene transcription.

Published
2001
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15. GATA-6: the proliferation stops here: cell proliferation in glomerular mesangial and vascular smooth muscle cells.

Author

Morrisey EE

Subjects
Cell Cycle, Cell Division drug effects, Cell Division physiology, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinases antagonists & inhibitors, Cyclins metabolism, Cyclins pharmacology, DNA-Binding Proteins pharmacology, E2F Transcription Factors, Enhancer Elements, Genetic, Enzyme Inhibitors metabolism, Enzyme Inhibitors pharmacology, GATA6 Transcription Factor, Glomerular Mesangium cytology, Glomerulonephritis metabolism, Glomerulonephritis pathology, Muscle, Smooth, Vascular cytology, Retinoblastoma-Binding Protein 1, Transcription Factors pharmacology, Carrier Proteins, Cell Cycle Proteins, DNA-Binding Proteins metabolism, Glomerular Mesangium metabolism, Muscle, Smooth, Vascular metabolism, Transcription Factors metabolism
Published
2000
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16. The gene encoding the mitogen-responsive phosphoprotein Dab2 is differentially regulated by GATA-6 and GATA-4 in the visceral endoderm.

Author

Morrisey EE, Musco S, Chen MY, Lu MM, Leiden JM, and Parmacek MS

Subjects
3T3 Cells, Adaptor Proteins, Signal Transducing, Animals, Apoptosis Regulatory Proteins, Base Sequence, Cell Differentiation, DNA, Complementary metabolism, DNA-Binding Proteins physiology, GATA4 Transcription Factor, GATA6 Transcription Factor, Genes, Tumor Suppressor, Humans, In Situ Hybridization, Mice, Molecular Sequence Data, Phosphoproteins genetics, Plasmids, Promoter Regions, Genetic, Protein Structure, Tertiary, Recombinant Fusion Proteins metabolism, Stem Cells cytology, Transcription Factors physiology, Transcription, Genetic, Transcriptional Activation, Tumor Suppressor Proteins, Adaptor Proteins, Vesicular Transport, DNA-Binding Proteins metabolism, Endoderm metabolism, Gene Expression Regulation, Developmental, Phosphoproteins metabolism, Proteins, Transcription Factors metabolism
Abstract

Gene targeting studies have demonstrated that the zinc finger transcription factor GATA-6 lies upstream in a transcriptional cascade that controls differentiation of the visceral endoderm. To understand the function of GATA-6 in the visceral endoderm and to identify genes regulated by GATA-6 in this tissue, subtractive hybridization was performed using template cDNAs derived from differentiated wild-type embryonic stem (ES) cells and GATA-6(-/-) ES cells, respectively. These analyses revealed that the gene encoding Dab2, a mitogen-responsive phosphoprotein, is differentially expressed in wild-type and GATA-6-deficient ES cells. Consistent with these findings, Dab2 is expressed in the visceral endoderm of wild-type embryos but not in the visceral endoderm of GATA-6-deficient embryos. Cotransfection experiments demonstrate that the human Dab2 promoter can be transactivated by forced expression of GATA-6 in NIH-3T3 cells. In contrast, forced expression of GATA-4 does not transactivate the human Dab2 promoter and Dab2 is expressed in the visceral endoderm of GATA-4 null embryos. Surprisingly, the specificity of GATA-6-induced transactivation of the Dab2 promoter is not mediated through its zinc finger DNA-binding domain. Taken together, these data demonstrate that the mitogen-responsive phosphoprotein Dab2 is a downstream target of GATA-6 in the visceral endoderm. Moreover, these data demonstrate that molecular mechanisms have evolved that direct, and distinguish, the functional specificity of GATA family members when they are developmentally coexpressed.

Published
2000
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17. GATA-5: a transcriptional activator expressed in a novel temporally and spatially-restricted pattern during embryonic development.

Author

Morrisey EE, Ip HS, Tang Z, Lu MM, and Parmacek MS

Subjects
3T3 Cells, Amino Acid Sequence, Animals, Base Sequence, COS Cells, Cloning, Molecular, DNA, Complementary, Embryonic and Fetal Development, GATA5 Transcription Factor, Gastrula chemistry, Heart embryology, Lung embryology, Mesoderm chemistry, Mice, Molecular Sequence Data, Muscle, Smooth chemistry, Muscle, Smooth cytology, Organ Specificity, RNA, Messenger analysis, Sequence Homology, Amino Acid, DNA-Binding Proteins genetics, Gene Expression Regulation, Developmental physiology, Trans-Activators genetics, Transcription Factors genetics
Abstract

Members of the GATA family of zinc finger transcription factors regulate critical steps of cellular differentiation during vertebrate development. In the studies described in this report, we have isolated and functionally characterized the murine GATA-5 cDNA and protein and defined the temporal and spatial pattern of GATA-5 gene expression during mammalian development. The amino terminus of the mouse GATA-5 protein shares high level amino acid sequence identity with the murine GATA-4 and -6 proteins, but not with other members of the GATA family. GATA-5 binds to the functionally important CEF-1 nuclear protein binding site in the cardiac-specific slow/cardiac troponin C (cTnC) transcriptional enhancer and overexpression of GATA-5 transactivates the cTnC enhancer in noncardiac muscle cell lines. During embryonic and postnatal development, the pattern of GATA-5 gene expression differs significantly from that of other GATA family members. In the primitive streak embryo, GATA-5 mRNA is detectable in the precardiac mesoderm. Within the embryonic heart, the GATA-5 gene is expressed within the atrial and ventricular chambers (ED 9.5), becomes restricted to the atrial endocardium (ED 12.5), and is subsequently not expressed in the heart during late fetal and postnatal development. Moreover, coincident with the earliest steps in lung development, only the GATA-5 gene is expressed within the pulmonary mesenchyme. Finally, the GATA-5 gene is expressed in tissue-restricted subsets of smooth muscle cells (SMCs), including bronchial SMCs and SMCs in the bladder wall. These data are consistent with a model in which GATA-5 performs a unique temporally and spatially restricted function in the embryonic heart and lung. Moreover, these data suggest that GATA-5 may play an important role in the transcriptional program(s) that underlies smooth muscle cell diversity.

Published
1997
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18. GATA-6: a zinc finger transcription factor that is expressed in multiple cell lineages derived from lateral mesoderm.

Author

Morrisey EE, Ip HS, Lu MM, and Parmacek MS

Subjects
Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Cardiovascular System embryology, Cell Lineage genetics, Clone Cells, DNA, Complementary isolation & purification, Digestive System embryology, GATA6 Transcription Factor, Lung embryology, Mice, Molecular Sequence Data, Muscle, Skeletal embryology, Muscle, Smooth, Vascular embryology, RNA analysis, Rats, Troponin genetics, Troponin C, Urogenital System embryology, DNA-Binding Proteins genetics, Gene Expression Regulation, Developmental, Mesoderm physiology, Transcription Factors genetics, Zinc Fingers genetics
Abstract

Members of the GATA family of zinc finger transcription factors play important roles in the development of several mesodermally derived cell lineages. In the studies described in this report, we have isolated and functionally characterized the murine GATA-6 cDNA and protein and defined the temporal and spatial patterns of GATA-6 gene expression during mammalian development. The GATA-6 and -4 proteins share high-level amino acid sequence identity over a proline-rich region at the amino terminus of the protein that is not conserved in other GATA family members. GATA-6 binds to a functionally important nuclear protein binding site within the cardiac-specific cardiac troponin C (cTnC) transcriptional enhancer. Moreover, the cTnC promoter enhancer can be transactivated by overexpression of GATA-6 in noncardiac muscle cells. During early murine embryonic development, the patterns of GATA-6 and -4 gene expression are similar, with expression of GATA-6 restricted to the precardiac mesoderm, the embryonic heart tube, and the primitive gut. However, coincident with the onset of vasculogenesis and development of the respiratory and urogenital tracts, only the GATA-6 gene is expressed in arterial smooth muscle cells, the developing bronchi, and the urogenital ridge and bladder. These data are consistent with a model in which GATA-6 functions in concert with GATA-4 to direct tissue-specific gene expression during formation of the mammalian heart and gastrointestinal tract, but performs a unique function in programming lineage-restricted gene expression in the arterial system, the bladder, and the embryonic lung.

Published
1996
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