The FLT3 tyrosine kinase receptor inhibits neural stem/progenitor cell proliferation and collaborates with NGF to promote neuronal survival

Mol Cell Neurosci. 2001 Oct;18(4):381-93. doi: 10.1006/mcne.2001.1033.

Abstract

The FLT3 receptor tyrosine kinase (FLT3) was originally identified on hematopoietic stem cells (HSCs) and its ligand (FL) induces HSC proliferation. As stem cells originating from various tissues are more similar than once thought, the goal of this study was to determine whether neural stem cells express FLT3 and proliferate in response to FL. In fact, a subset of neural stem/progenitor cells does express FLT3, but contrary to our expectations, FL inhibited EGF and FGF-2 stimulated proliferation. Since FLT3 is expressed weakly by proliferative neuroepithelia but strongly by subsets of neurons in the CNS and PNS, we tested its ability to support neuronal survival. FL synergized with NGF to promote the survival of cultured DRG neurons, although it lacked any neurotrophic activity alone. We conclude that FL serves as an adjunct trophic factor in the nervous system, which differs from its role in the hematopoietic system.

Publication types

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

MeSH terms

  • Animals
  • Cell Division / physiology
  • Cell Survival / physiology
  • Cells, Cultured
  • Drug Synergism
  • Embryo, Mammalian / metabolism
  • Embryonic and Fetal Development
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Membrane Proteins / metabolism
  • Membrane Proteins / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Nerve Growth Factor / pharmacology
  • Nerve Growth Factor / physiology*
  • Nervous System / embryology
  • Neurons / cytology*
  • Neurons / physiology*
  • Proto-Oncogene Proteins / physiology*
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Spheroids, Cellular
  • Stem Cells / cytology*
  • fms-Like Tyrosine Kinase 3

Substances

  • Membrane Proteins
  • Proto-Oncogene Proteins
  • flt3 ligand protein
  • Nerve Growth Factor
  • Flt3 protein, mouse
  • Receptor Protein-Tyrosine Kinases
  • fms-Like Tyrosine Kinase 3