Identification of c-Kit receptor as a regulator of adult neural stem cells in the mammalian eye: interactions with Notch signaling

Dev Biol. 2004 Sep 1;273(1):87-105. doi: 10.1016/j.ydbio.2004.05.023.

Abstract

Neural stem cells are present in specific regions of the adult central nervous system (CNS). Recent evidence suggests that the ciliary epithelium (CE), a CNS derivative, in the adult mammalian eye, harbors a quiescent population of neural stem cells. Here, we report the identification of c-Kit signaling as one of the regulators of adult CE neural stem cells in vitro. c-Kit receptors are expressed in proliferating adult CE neural stem cells and colocalized with neural progenitor markers. Perturbation of c-Kit signaling influences the self-renewal and differentiation of CE neural stem cells, thus demonstrating the role of c-Kit signaling in the maintenance of these cells. In addition, we observed an influence of c-Kit-mediated signaling on the expression of Notch1, another critical regulator of neural stem cells. Our observations suggest that, given the importance of preservation of a stem cell pool for generating different cell types at different times, multiple signaling pathways act in concert for the maintenance of neural stem cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bromodeoxyuridine
  • Ciliary Body / cytology*
  • DNA Primers
  • DNA, Complementary / genetics
  • Green Fluorescent Proteins
  • Immunohistochemistry
  • Luminescent Proteins
  • Protein Array Analysis
  • Proto-Oncogene Proteins c-kit / metabolism*
  • RNA / genetics
  • Rats
  • Receptor, Notch1
  • Receptors, Cell Surface / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • Stem Cells / metabolism*
  • Transcription Factors / metabolism*
  • Tubulin

Substances

  • DNA Primers
  • DNA, Complementary
  • Luminescent Proteins
  • Notch1 protein, rat
  • Receptor, Notch1
  • Receptors, Cell Surface
  • Transcription Factors
  • Tubulin
  • Green Fluorescent Proteins
  • RNA
  • Proto-Oncogene Proteins c-kit
  • Bromodeoxyuridine