Dynamic Lkb1-TORC1 signaling as a possible mechanism for regulating the endoderm-intestine transition

Authors

  • Kathryn E. Marshall,

    1. Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin
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  • Amber J. Tomasini,

    1. Departments of Pediatrics, Gastroenterology Section, Medical College of Wisconsin, Milwaukee, Wisconsin
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  • Khadijah Makky,

    1. Departments of Pediatrics, Gastroenterology Section, Medical College of Wisconsin, Milwaukee, Wisconsin
    Current affiliation:
    1. Department of Biomedical Sciences, College of Health Sciences, Marquette University, Schroeder Complex 426, P.O. Box 1881, Milwaukee, WI 53201
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  • Suresh N. Kumar,

    1. Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin
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  • Alan N. Mayer

    Corresponding author
    1. Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin
    2. Departments of Pediatrics, Gastroenterology Section, Medical College of Wisconsin, Milwaukee, Wisconsin
    • Department of Pediatrics, Gastroenterology Section, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226
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Errata

This article is corrected by:

  1. Errata: Dynamic lkb1-TORC1 signaling as a possible mechanism for regulating the endoderm-intestine transition Volume 240, Issue 2, 459, Article first published online: 3 January 2011

Abstract

The intestinal epithelium arises from undifferentiated endoderm via a developmental program known as the endoderm-intestine transition (EIT). Previously we found that the target of rapamycin complex 1 (TORC1) regulates intestinal growth and differentiation during the EIT in zebrafish. Here we address a possible role for the tumor-suppressor kinase Lkb1 in regulating TORC1 in this context. We find that TORC1 activity is transiently upregulated during the EIT in both zebrafish and mouse. Concomitantly, Lkb1 becomes transiently localized to the nucleus, suggesting that these two phenomena may be linked. Morpholino-mediated knockdown of lkb1 stimulated intestinal growth via upregulation of TORC1, and also induced precocious intestine-specific gene expression in the zebrafish gut epithelium. Knockdown of tsc2, which acts downstream of lkb1, likewise induced early expression of intestine-specific genes. These data suggest that programmed localization of Lkb1 could represent a novel mechanism for regulating the EIT during intestinal development in vertebrates. Developmental Dynamics 239:3000–3012, 2010. © 2010 Wiley-Liss, Inc.

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