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Dynamic Lkb1-TORC1 signaling as a possible mechanism for regulating the endoderm-intestine transition. Dev Dyn 2010 Nov;239(11):3000-12

Date

10/07/2010

Pubmed ID

20925120

Pubmed Central ID

PMC4420030

DOI

10.1002/dvdy.22437

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.

Author List

Marshall KE, Tomasini AJ, Makky K, N Kumar S, Mayer AN

Author

Suresh Kumar PhD Associate Professor in the Pathology department at Medical College of Wisconsin




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

Animals
Animals, Genetically Modified
Blotting, Western
Cell Differentiation
Embryo, Mammalian
Embryo, Nonmammalian
Endoderm
Fluorescent Antibody Technique
Gene Expression Regulation, Developmental
In Situ Hybridization
Intestines
Mice
Protein-Serine-Threonine Kinases
Reverse Transcriptase Polymerase Chain Reaction
Zebrafish
Zebrafish Proteins
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a