Age-dependent effects of TWEAK/Fn14 receptor activation on neural progenitor cells

J Neurosci Res. 2007 Dec;85(16):3535-44. doi: 10.1002/jnr.21443.


TWEAK/Fn14 signaling regulates progenitor cell proliferation, differentiation, and survival in multiple organ systems. This study examined the effects of TWEAK (tumor necrosis factor-like weak inducer of apoptosis) treatment on cultured mouse neural progenitor cells. The receptor for TWEAK is expressed by neural progenitor cells from the early embryonic stages through postnatal development. Although embryonic day 12 (E12) and postnatal day 1 (PN1) neural progenitor cells both express the receptor for TWEAK, TWEAK treatment of cultured E12 and PN1 progenitor cells resulted in age-dependent effects on proliferation and on neurite extension by neuronal progeny. TWEAK treatment did not alter proliferation of E12 neural progenitor cells but shifted PN1 progenitor cells toward cell-cycle phases G0 and G1 and reduced the rate at which they incorporated CldU. Conversely, the effects of TWEAK on axon elongation were more prominent in the earlier developmental stage. TWEAK induced extensive neurite outgrowth by the neuronal progeny of E12 but not PN1 progenitors. Treatment of the E12 progenitor cells with a TWEAK-neutralizing antibody repressed neurite extension, indicating that endogenous activation of this pathway may be required for neurite extension by the embryonic neuronal progeny. These studies indicate that TWEAK/Fn14 receptor activation exerts different effects on neural progenitor cells and their progeny depending on the developmental stage of the cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / physiology*
  • Animals
  • Animals, Newborn
  • Antibodies / pharmacology
  • Brain / embryology*
  • Cell Cycle / drug effects
  • Cell Cycle / physiology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / pharmacology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokine TWEAK
  • Gene Expression Regulation, Developmental / genetics
  • Growth Cones / drug effects
  • Growth Cones / metabolism
  • Growth Cones / ultrastructure
  • Mice
  • Neurons / metabolism*
  • Receptors, Tumor Necrosis Factor / agonists
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • TWEAK Receptor
  • Tumor Necrosis Factors / genetics
  • Tumor Necrosis Factors / metabolism*
  • Tumor Necrosis Factors / pharmacology


  • Antibodies
  • Cell Cycle Proteins
  • Cytokine TWEAK
  • Receptors, Tumor Necrosis Factor
  • TWEAK Receptor
  • Tnfrsf12a protein, mouse
  • Tnfsf12 protein, mouse
  • Tumor Necrosis Factors