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GATA4 regulates epithelial morphogenesis in the developing mouse stomach to promote establishment of a simple columnar epithelium

ABSTRACT: GATA4 regulates epithelial morphogenesis in the developing mouse stomach to promote establishment of a simple columnar epithelium

PROVIDER: PRJNA657525 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12440219.fastq.gz	Fastqsanger.gz
	SRR12440220.fastq.gz	Fastqsanger.gz
	SRR12440221.fastq.gz	Fastqsanger.gz
	SRR12440222.fastq.gz	Fastqsanger.gz
	SRR12440223.fastq.gz	Fastqsanger.gz

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Epithelial expressions of Gata4 and Sox2 regulate murine specification of the squamous–columnar junction via MAPK/ERK signaling

Project description:The squamous–columnar junction (SCJ) is a boundary consisting of precisely positioned transitional epithelium between the squamous and columnar epithelium. Transitional epithelium is a hotspot for precancerous lesions, and is therefore clinically important; however, the origins and physiological properties of transitional epithelium have not been fully elucidated. Here, by using mouse genetics, lineage tracing, and organoid culture, we examine the development of the SCJ in the mouse stomach, and thus define the unique features of transitional epithelium. We find that two transcription factors, encoded by Sox2 and Gata4, specify primitive transitional epithelium into squamous and columnar epithelium. The proximal–distal segregation of Sox2 and Gata4 expression establishes the boundary of the unspecified transitional epithelium between committed squamous and columnar epithelium. Mechanistically, Gata4-mediated expression of the morphogen Fgf10 in the distal stomach and Sox2-mediated Fgfr2 expression in the proximal stomach induce the intermediate regional activation of MAPK/ERK, which prevents the differentiation of transitional epithelial cells at the SCJ boundary. Our results have implications for tissue regeneration and tumorigenesis, which are related to the SCJ.

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Single-cell RNA-seq characterization of columnar epithelial cells in mouse stomach.

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Project description:GATA4 facilitates its function as a transcriptional regulator by binding to promoter and enhancer regions of target genes in the glandular stomach.

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GATA4 Controls Epithelial Morphogenesis in the Developing Stomach to Promote Establishment of Glandular Columnar Epithelium.

Project description:Background & aimsThe transcription factor GATA4 is broadly expressed in nascent foregut endoderm. As development progresses, GATA4 is lost in the domain giving rise to the stratified squamous epithelium of the esophagus and forestomach (FS), while it is maintained in the domain giving rise to the simple columnar epithelium of the hindstomach (HS). Differential GATA4 expression within these domains coincides with the onset of distinct tissue morphogenetic events, suggesting a role for GATA4 in diversifying foregut endoderm into discrete esophageal/FS and HS epithelial tissues. The goal of this study was to determine how GATA4 regulates differential morphogenesis of the mouse gastric epithelium.MethodsWe used a Gata4 conditional knockout mouse line to eliminate GATA4 in the developing HS and a Gata4 conditional knock-in mouse line to express GATA4 in the developing FS.ResultsWe found that GATA4-deficient HS epithelium adopted a FS-like fate, and conversely, that GATA4-expressing FS epithelium adopted a HS-like fate. Underlying structural changes in these epithelia were broad changes in gene expression networks attributable to GATA4 directly activating or repressing expression of HS or FS defining transcripts. Our study implicates GATA4 as having a primary role in suppressing an esophageal/FS transcription factor network during HS development to promote columnar epithelium. Moreover, GATA4-dependent phenotypes in developmental mutants reflected changes in gene expression associated with Barrett's esophagus.ConclusionsThis study demonstrates that GATA4 is necessary and sufficient to activate the development of simple columnar epithelium, rather than stratified squamous epithelium, in the embryonic stomach. Moreover, similarities between mutants and Barrett's esophagus suggest that developmental biology can provide insight into human disease mechanisms.

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GATA4 regulates epithelial morphogenesis in the developing mouse stomach to promote establishment of a simple columnar epithelium

Project description:This SuperSeries is composed of the SubSeries listed below.

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GATA4 genome binding targets in adult mouse stomach

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mRNA sequencing of esophageal cells and columnar cells from different tissues

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