Requirement of Math1 for secretory cell lineage commitment in the mouse intestine

Science. 2001 Dec 7;294(5549):2155-8. doi: 10.1126/science.1065718.

Abstract

The mouse small intestinal epithelium consists of four principal cell types deriving from one multipotent stem cell: enterocytes, goblet, enteroendocrine, and Paneth cells. Previous studies showed that Math1, a basic helix-loop-helix (bHLH) transcription factor, is expressed in the gut. We find that loss of Math1 leads to depletion of goblet, enteroendocrine, and Paneth cells without affecting enterocytes. Colocalization of Math1 with Ki-67 in some proliferating cells suggests that secretory cells (goblet, enteroendocrine, and Paneth cells) arise from a common progenitor that expresses Math1, whereas absorptive cells (enterocytes) arise from a progenitor that is Math1-independent. The continuous rapid renewal of these cells makes the intestinal epithelium a model system for the study of stem cell regeneration and lineage commitment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation*
  • Cell Division
  • Cell Lineage
  • Enterocytes / cytology
  • Enteroendocrine Cells / cytology
  • Gene Expression
  • Goblet Cells / cytology
  • Helix-Loop-Helix Motifs
  • Heterozygote
  • Homeodomain Proteins / metabolism
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / embryology
  • Intestinal Mucosa / metabolism*
  • Intestine, Large / cytology
  • Intestine, Large / embryology
  • Intestine, Small / cytology
  • Intestine, Small / embryology
  • Ki-67 Antigen / analysis
  • Membrane Proteins / metabolism
  • Mice
  • Paneth Cells / cytology
  • Paneth Cells / metabolism
  • Protein Precursors / analysis
  • Receptors, Notch
  • Signal Transduction
  • Stem Cells / cytology*
  • Transcription Factor HES-1
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*

Substances

  • Atoh1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Hes1 protein, mouse
  • Homeodomain Proteins
  • Ki-67 Antigen
  • Membrane Proteins
  • Protein Precursors
  • Receptors, Notch
  • Transcription Factor HES-1
  • Transcription Factors
  • cryptdin