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Hepatocyte nuclear factor 4alpha is essential for embryonic development of the mouse colon. Gastroenterology 2006 Apr;130(4):1207-20



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2-s2.0-33646477296   121 Citations


BACKGROUND & AIMS: Hepatocyte nuclear factor 4 alpha (HNF4alpha) is a transcription factor that has been shown to be required for hepatocyte differentiation and development of the liver. It has also been implicated in regulating expression of genes that act in the epithelium of the lower gastrointestinal tract. This implied that HNF4alpha might be required for development of the gut.

METHODS: Mouse embryos were generated in which Hnf4a was ablated in the epithelial cells of the fetal colon by using Cre-loxP technology. Embryos were examined by using a combination of histology, immunohistochemistry, DNA microarray, reverse-transcription polymerase chain reaction, electrophoretic mobility shift assays, and chromatin immunoprecipitation analyses to define the consequences of loss of HNF4alpha on colon development.

RESULTS: Embryos were recovered at E18.5 that lacked HNF4alpha in their colons. Although early stages of colonic development occurred, HNF4alpha-null colons failed to form normal crypts. In addition, goblet-cell maturation was perturbed and expression of an array of genes that encode proteins with diverse roles in colon function was disrupted. Several genes whose expression in the colon was dependent on HNF4alpha contained HNF4alpha-binding sites within putative transcriptional regulatory regions and a subset of these sites were occupied by HNF4alpha in vivo.

CONCLUSIONS: HNF4alpha is a transcription factor that is essential for development of the mammalian colon, regulates goblet-cell maturation, and is required for expression of genes that control normal colon function and epithelial cell differentiation.

Author List

Garrison WD, Battle MA, Yang C, Kaestner KH, Sladek FM, Duncan SA


Michele A. Battle PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Count
Embryo, Mammalian
Embryonic Development
Gastric Mucosa
Gene Expression
Goblet Cells
Hepatocyte Nuclear Factor 4
Intestinal Mucosa
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Reference Values
Reverse Transcriptase Polymerase Chain Reaction