Extensive neuronal localization and neurotrophic function of fibroblast growth factor 8 in the nervous system

Brain Res. 2001 Sep 7;912(2):105-15. doi: 10.1016/s0006-8993(01)02726-3.

Abstract

Fibroblast growth factor (FGF) 8 has been well established to play a critical role in the early development of the central nervous system (CNS). We report here extensive neuronal localization and neurotrophic function of FGF8 in the nervous system. In sections of mouse embryos at E10.5, FGF8 was immunohistochemically found in neurons at the marginal zones of the CNS and in the dorsal root ganglia (DRG). Neuronal localization of FGF8 was marked at later embryonic stages and in adults, involving most of the central and peripheral neurons, including intermuscular enteric neurons, DRGs, and paraaortic sympathetic ganglia. Functionally, FGF8 promoted neurite outgrowth in human neuroblastoma SK-N-MC cells as well as in rat pheochromocytoma PC12 cells, suggesting that FGF8 acts as a neurotrophic factor. FGF8 also supported neuronal survival and differentiation in cultured human neural progenitor cells. In a cell growth assay, treatment with 50 ng/ml FGF8 on human cultured neuroblastoma SK-N-MC and IMR32 cells attenuated the growth of both. In accordance with these in vitro findings, the immunohistochemical analysis on human neurological diseases showed that FGF8 expression is evident in differentiating histological types of neuroblastoma and ganglioneuroblastoma, and that the levels of FGF8 immunoreactivity in the substantia nigra from Parkinson's disease are significantly lower than those in age-matched controls. Taken together, the present findings strongly suggest that FGF8 acts as a more generalized neurotrophic factor than previously reported.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Division / drug effects
  • Cell Division / physiology
  • Child, Preschool
  • Female
  • Fetus
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • Fibroblast Growth Factors / pharmacology
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Glioblastoma / physiopathology
  • Humans
  • Immunohistochemistry
  • Infant
  • Male
  • Medulloblastoma / metabolism
  • Medulloblastoma / pathology
  • Medulloblastoma / physiopathology
  • Mice
  • Mice, Inbred ICR
  • Nervous System / cytology
  • Nervous System / embryology
  • Nervous System / metabolism*
  • Nervous System Neoplasms / metabolism*
  • Nervous System Neoplasms / pathology
  • Nervous System Neoplasms / physiopathology
  • Neurites / drug effects
  • Neurites / metabolism
  • Neurites / ultrastructure
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Neuroblastoma / physiopathology
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / physiopathology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • PC12 Cells / cytology
  • PC12 Cells / drug effects
  • PC12 Cells / metabolism
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology
  • RNA, Messenger / metabolism
  • Rats
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism

Substances

  • FGF8 protein, human
  • Fgf8 protein, mouse
  • Fgf8 protein, rat
  • RNA, Messenger
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors