Fibroblast growth factor-mediated proliferation of central nervous system precursors depends on endogenous production of insulin-like growth factor I.
Fibroblast growth factor stimulates proliferation and subsequent differentiation of precursor cells isolated from the neuroepithelium of embryonic day 10 mice in vitro. Here we show that fibroblast growth factor-induced proliferation is dependent on the presence of insulin-like growth factors (IGFs) and that IGF-I is endogenously produced by the neuroepithelial cells. Blocking of endogenous IGF-I activity with anti-IGF-I antibodies results in complete inhibition of fibroblast growth factor-mediated proliferation and in cell death. IGF-I alone acts as a survival agent. These observations correlate with the detection of transcripts for IGF-I and basic fibroblast growth factor in freshly isolated neuroepithelium and are consistent with an autocrine action of these factors in early brain development in vivo.
Drago
J
J
Walter and Eliza Hall Institute of Medical Research, Royal Parade, Parkville, Victoria, Australia.
Murphy
M
M
Carroll
S M
SM
Harvey
R P
RP
Bartlett
P F
PF
D000818:Animals; D000906:Antibodies; D001345:Autoradiography; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D004622:Embryo, Mammalian; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D007700:Kinetics; D008636:Mesencephalon / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D011994:Recombinant Proteins / Q000494:pharmacology; D013687:Telencephalon / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D000906:Antibodies; D011994:Recombinant Proteins; D014316:Tritium; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D013936:Thymidine