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Gastroenterology. 1998 Aug;115(2):381-7.

Misexpression of the pancreatic homeodomain protein IDX-1 by the Hoxa-4 promoter associated with agenesis of the cecum.

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  • 1Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston and Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

BACKGROUND & AIMS:

The endoderm-specific homeodomain transcription factor IDX-1 is critical for pancreas development and for the regulation of islet cell-specific genes. During development, IDX-1 is expressed in the epithelial cells of the endoderm in the pancreatic anlage of the foregut. The aim of this study was to determine whether IDX-1 may have potential properties of a master homeotic determinant of pancreas and/or gut development.

METHODS:

Transgenic mice were generated in which the expression of IDX-1 was misdirected by a promoter of the mesoderm-specific homeodomain protein Hoxa-4 known to express in the stomach and hindgut during development. The expectation was the formation of ectopic pancreatic tissue or alterations of gut patterning or morphology.

RESULTS:

Although no ectopic induction of pancreatic markers was found in these transgenic mice, they manifested an altered midgut-hindgut union and agenesis of the cecum. Further, IDX-1 binds to the gut-specific homeodomain protein Cdx-2 and inhibits transactivation of the sucrase-isomaltase promoter by Cdx-2.

CONCLUSIONS:

These findings further support the emerging understanding that interactions among different classes of homeodomain proteins, expressed in a spatially and temporally restricted manner during development, determine the pattern of organogenesis. A possible mechanism for the dysmorphogenesis of the proximal colon may be an inhibition of Cdx-2 actions by IDX-1.

PMID:
9679043
[PubMed - indexed for MEDLINE]
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