title: Increased innervation of forebrain targets by midbrain dopaminergic neurons in the absence of FGF-2.
abstract: Fibroblast growth factors (FGFs) regulate development and maintenance, and reduce vulnerability of neurons. FGF-2 is essential for survival of midbrain dopaminergic (DA) neurons and is responsible for their dysplasia and disease-related degeneration. We previously reported that FGF-2 is involved in adequate forebrain (FB) target innervation by these neurons in an organotypic co-culture model. It remains unclear, how this ex-vivo phenotype relates to the in vivo situation, and which FGF-related signaling pathway is involved in this process. Here, we demonstrate that lack of FGF-2 results in an increased volume of the striatal target area in mice. We further add evidence that the low molecular weight (LMW) FGF-2 isoform is responsible for this phenotype, as this isoform is predominantly expressed in the embryonic ventral midbrain (VM) as well as in postnatal striatum (STR) and known to act via canonical transmembrane FGF receptor (FGFR) activation. Additionally, we confirm that the phenotype with an enlarged FB-target area by DA neurons can be mimicked in an ex-vivo explant model by inhibiting the canonical FGFR signaling, which resulted in decreased extracellular signal-regulated kinase (ERK) activation, while AKT activation remained unchanged.
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Rumpel
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Baron
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ratzka
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany; Center for Systems Neuroscience (ZSN), Bünteweg 2, 30559 Hannover, Germany.
authors.forename: M-L
authors.initials: ML
authors.lastname: Schröder
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hohmann
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Effenberg
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany; Center for Systems Neuroscience (ZSN), Bünteweg 2, 30559 Hannover, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Claus
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany; Center for Systems Neuroscience (ZSN), Bünteweg 2, 30559 Hannover, Germany. Electronic address: grothe.claudia@mh-hannover.de.
authors.forename: C
authors.initials: C
authors.lastname: Grothe
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D016548:Prosencephalon; D020033:Protein Isoforms / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D016222:Fibroblast Growth Factor 2; D014446:Tyrosine 3-Monooxygenase; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051057:Proto-Oncogene Proteins c-akt
keywords: FGF; dopaminergic neuron; neural development; neurotrophic factor; ventral midbrain