Fibroblast growth factor 2 negatively regulates the induction of neuronal progenitors from neural stem cells.
Fibroblast growth factor 2 (FGF2) exhibits pleiotropic functions during embryogenesis. In neural development, both pro- and antineurogenic activities of FGF2 have been described in the differentiation of neuronal progenitors into postmitotic neurons. We used cultured neural stem cells (NSCs) derived from rat embryonic day 14.5 cortex to determine the FGF2 effect on the induction of early neuronal progenitors. Our data showed that the presence of FGF2 during serum-induced differentiation of NSCs reduced the number of Tuj1(+) neurons. A bromodeoxyuridine (BrdU)/Tuj1 double-labeling assay and expression analyses of the pro- and antineurogenic basic helix-loop-helix (bHLH) factors showed that FGF2 blocked the generation of early neuronal progenitors, but not the cell-cycle exit of dividing neurons. This negative regulation of neuronal induction by FGF2 was associated with the persistent expression of an antineurogenic bHLH, hairy and enhancer of split (HES)-1. A gene-profiling study demonstrated that the developmental programs underlying neuronal differentiation were altered as a whole and identified several developmentally regulated, neural-enriched genes. This work shows that FGF2 exerts an antineurogenic effect during the developmental window when neuronal progenitors are first induced from NSCs. It also provides a novel experimental system that can be used to prospectively identify genes expressed at different stages of neuronal differentiation.
Tsai
Robert Y L
RY
Center for Cancer Biology and Nutrition, Alkek Institute of Biosciences and Technology, Texas A and M University System Health Science Center, Houston, Texas 77030, USA. rtsai@ibt.tamhsc.edu
Kim
Seokwoon
S
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D025461:Feedback, Physiological / Q000187:drug effects / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D000072056:Transcription Factor HES-1; D014404:Tubulin / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D016222:Fibroblast Growth Factor 2; D018398:Homeodomain Proteins; D000072056:Transcription Factor HES-1; D014404:Tubulin; C489735:Hes1 protein, rat; C462941:beta3 tubulin, mouse