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Fibroblast growth factor 2 regulates dopaminergic neuron development in vivo
Author(s) -
Ratzka Andreas,
Baron Olga,
Stachowiak Michal K.,
Grothe Claudia
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07768.x
Subject(s) - pars compacta , neurogenesis , biology , substantia nigra , fibroblast growth factor , microbiology and biotechnology , dopaminergic , neurotrophic factors , ventral tegmental area , neuroscience , embryonic stem cell , dopamine , genetics , receptor , gene
J. Neurochem. (2012) 122 , 94–105. 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.