title: Significance of F3/Contactin gene expression in cerebral cortex and nigrostriatal development.
abstract: F3/Contactin is a neuronal surface glycoprotein, which plays a general role in neural development and, in particular, in neuronal and oligodendrocyte differentiation. In a previous study using the F3/EGFP transgenic mice, which express an EGFP reporter under control of the regulatory region from the mouse F3/Contactin gene, the activation of the F3/Contactin promoter was found to correlate with granule and Purkinje neuron differentiation in developing cerebellar cortex. Here we report that in developing cerebral cortex and basal ganglia the F3/Contactin gene is mostly activated during early commitment of neuronal precursors, thus indicating a region-specific profile of its developmental activation. We also report that, in the same structures of F3/EGFP mice, a downregulation of the endogenous F3/Contactin gene occurs, which correlates with upregulation of the dopaminergic phenotype and with locomotor pattern abnormalities. Therefore, F3/EGFP transgenic mice exhibit morphological and functional phenotypes recapitulating those arising from imbalance of the striatal dopaminergic pathway. As for the underlying mechanisms, we postulate that in F3/EGFP mice F3/Contactin downregulation results from the ability of transgene promoter sequences to interfere with the activation of the endogenous gene, thus realizing an F3/Contactin knockdown model, while dopaminergic upregulation is consistent with a general F3/Contactin inhibitory effect on the neuronal phenotype.
authors.affiliation: Department of Basic Medical Sciences, Medical School, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Massaro
authors.forename: Antonella
authors.initials: A
authors.lastname: Bizzoca
authors.forename: Patrizia
authors.initials: P
authors.lastname: Corsi
authors.forename: Marco F
authors.initials: MF
authors.lastname: Pinto
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Carratù
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Gennarini
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism*; D058967:Contactin 1 / Q000235:genetics* / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins; D013378:Substantia Nigra / Q000254:growth & development / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D058967:Contactin 1; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins