Distinct levels of Notch activity for commitment and terminal differentiation of stem cells in the adult fly intestine

Development. 2011 Nov;138(21):4585-95. doi: 10.1242/dev.065292. Epub 2011 Sep 28.

Abstract

Tight regulation of self-renewal and differentiation of adult stem cells ensures that tissues are properly maintained. In the Drosophila intestine, both commitment, i.e. exit from self-renewal, and terminal differentiation are controlled by Notch signaling. Here, we show that distinct requirements for Notch activity exist: commitment requires high Notch activity, whereas terminal differentiation can occur with lower Notch activity. We identified the gene GDP-mannose 4,6-dehydratase (Gmd), a modulator of Notch signaling, as being required for commitment but dispensable for terminal differentiation. Gmd loss resulted in aberrant, self-renewing stem cell divisions that generated extra ISC-like cells defective in Notch reporter activation, as well as wild-type-like cell divisions that produced properly terminally differentiated cells. Lowering Notch signaling using additional genetic means, we provided further evidence that commitment has a higher Notch signaling requirement than terminal differentiation. Our work suggests that a commitment requirement for high-level Notch activity safeguards the stem cells from loss through differentiation, revealing a novel role for the importance of Notch signaling levels in this system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / anatomy & histology*
  • Drosophila melanogaster / physiology*
  • Fucosyltransferases / genetics
  • Fucosyltransferases / metabolism
  • Genes, Reporter
  • Hydro-Lyases / genetics
  • Hydro-Lyases / metabolism
  • Intestines / cytology*
  • Intestines / physiology
  • Mutation
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Signal Transduction / physiology
  • Stem Cells / cytology
  • Stem Cells / physiology*

Substances

  • Drosophila Proteins
  • Receptors, Notch
  • Fucosyltransferases
  • O-fucosyltransferase 1, Drosophila
  • Hydro-Lyases