Disruption of hedgehog signaling reveals a novel role in intestinal morphogenesis and intestinal-specific lipid metabolism in mice

Li Chun Wang, Fatiha Nassir, Zhong Ying Liu, Leona Ling, Frank Kuo, Thomas Crowell, Dian Olson, Nicholas O. Davidson, Linda C. Burkly

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Background & Aims: The hedgehog (hh) signaling pathway has been shown to play crucial roles in the development of embryonic gut. However, its role in intestinal development and function beyond the embryonic stage is still undefined. Methods: Expression of hh and its receptor, Patched, were examined by Western blot and X-gal staining. An anti-hh monoclonal antibody was administered into developing embryos or postnatal mice and histologic analyses were performed. Effects on lipid metabolism were examined by Oil Red O and Sudan III stainings, messenger RNA (mRNA) analysis, and electron microscopy. Serum apolipoprotein IV level, a marker for lipid absorption, was quantified by Western blot. Results: Mice receiving anti-hh monoclonal antibody in utero or after birth exhibited progressive runting and died before weaning. Histology revealed hyperproliferation of intestinal crypt epithelial cells and disorganization of the villi with prominent vacuolation and accumulation of neutral lipid. Fecal fat microscopy revealed numerous large fat droplets. Intestinal mRNA abundance of 2 candidate genes involved in lipid transport, mtp and apob, was unchanged, although serum levels of apolipoprotein A-IV were reduced. Conclusions: Abnormal villus structure, lipid-filled enterocytes, and fatty stools in anti-hh monoclonal antibody-treated mice indicate a novel role for hh signaling in intestinal morphogenesis and lipid transport in postnatal mice.

Original languageEnglish
Pages (from-to)469-482
Number of pages14
JournalGastroenterology
Volume122
Issue number2
DOIs
StatePublished - Feb 2002

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