Notch lineages and activity in intestinal stem cells determined by a new set of knock-in mice

PLoS One. 2011;6(10):e25785. doi: 10.1371/journal.pone.0025785. Epub 2011 Oct 3.

Abstract

The conserved role of Notch signaling in controlling intestinal cell fate specification and homeostasis has been extensively studied. Nevertheless, the precise identity of the cells in which Notch signaling is active and the role of different Notch receptor paralogues in the intestine remain ambiguous, due to the lack of reliable tools to investigate Notch expression and function in vivo. We generated a new series of transgenic mice that allowed us, by lineage analysis, to formally prove that Notch1 and Notch2 are specifically expressed in crypt stem cells. In addition, a novel Notch reporter mouse, Hes1-EmGFP(SAT), demonstrated exclusive Notch activity in crypt stem cells and absorptive progenitors. This roster of knock-in and reporter mice represents a valuable resource to functionally explore the Notch pathway in vivo in virtually all tissues.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation
  • Cell Lineage*
  • Clone Cells
  • Enterocytes / cytology
  • Enterocytes / metabolism
  • Gene Knock-In Techniques*
  • Gene Targeting
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Integrases / metabolism
  • Intestines / cytology*
  • Kinetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microvilli / metabolism
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / metabolism
  • Receptors, Notch / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Stem Cells / cytology*
  • Stem Cells / metabolism*
  • Transcription Factor HES-1
  • Transcription, Genetic

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Hes1 protein, mouse
  • Homeodomain Proteins
  • Receptors, Notch
  • Transcription Factor HES-1
  • Cre recombinase
  • Integrases