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

Dev Dyn. 2010 Nov;239(11):3000-12. doi: 10.1002/dvdy.22437.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Animals
  • Animals, Genetically Modified
  • Blotting, Western
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Embryo, Mammalian / metabolism
  • Embryo, Nonmammalian / metabolism
  • Endoderm / cytology*
  • Endoderm / metabolism*
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental
  • In Situ Hybridization
  • Intestines / cytology*
  • Intestines / embryology*
  • Mice
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / physiology


  • Zebrafish Proteins
  • Protein Serine-Threonine Kinases
  • Stk11 protein, mouse
  • AMP-Activated Protein Kinases