title: Fibroblast growth factor 2 regulates dopaminergic neuron development in vivo.
abstract: Fibroblast growth factor 2 (FGF-2) is a neurotrophic factor participating in regulation of proliferation, differentiation, apoptosis and neuroprotection in the central nervous system. With regard to dopaminergic (DA) neurons of substantia nigra pars compacta (SNpc), which degenerate in Parkinson's disease, FGF-2 improves survival of mature DA neurons in vivo and regulates expansion of DA progenitors in vitro. To address the physiological role of FGF-2 in SNpc development, embryonic (E14.5), newborn (P0) and juvenile (P28) FGF-2-deficient mice were investigated. Stereological quantification of DA neurons identified normal numbers in the ventral tegmental area, whereas the SNpc of FGF-2-deficient mice displayed a 35% increase of DA neurons at P0 and P28, but not at earlier stage E14.5. Examination of DA marker gene expression by quantitative RT-PCR and in situ hybridization revealed a normal patterning of embryonic ventral mesencephalon. However, an increase of proliferating Lmx1a DA progenitors in the subventricular zone of the ventral mesencephalon of FGF-2-deficient embryos indicated altered cell cycle progression of neuronal progenitors. Increased levels of nuclear FgfR1 in E14.5 FGF-2-deficient mice suggest alterations of integrative nuclear FgfR1 signaling (INFS). In summary, FGF-2 restricts SNpc DA neurogenesis in vivo during late stages of embryonic development.
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ratzka
authors.forename: Olga
authors.initials: O
authors.lastname: Baron
authors.forename: Michal K
authors.initials: MK
authors.lastname: Stachowiak
authors.forename: Claudia
authors.initials: C
authors.lastname: Grothe
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning / Q000235:genetics; D001973:Bromodeoxyuridine; D002452:Cell Count; D016923:Cell Death / Q000235:genetics; D059290:Dopaminergic Neurons / Q000502:physiology*; D004622:Embryo, Mammalian; D016222:Fibroblast Growth Factor 2 / Q000172:deficiency / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013378:Substantia Nigra / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D014157:Transcription Factors / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology* / Q000196:embryology / Q000254:growth & development
chemical_list: D060850:LIM-Homeodomain Proteins; C489692:Lmx1a protein, mouse; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; D014446:Tyrosine 3-Monooxygenase; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; D001973:Bromodeoxyuridine