title: Transgenic mice expressing F3/contactin from the TAG-1 promoter exhibit developmentally regulated changes in the differentiation of cerebellar neurons.
abstract: F3/contactin (CNTN1) and TAG-1 (CNTN2) are closely related axonal glycoproteins that are differentially regulated during development. In the cerebellar cortex TAG-1 is expressed first as granule cell progenitors differentiate in the premigratory zone of the external germinal layer. However, as these cells begin radial migration, TAG-1 is replaced by F3/contactin. To address the significance of this differential regulation, we have generated transgenic mice in which F3/contactin expression is driven by TAG-1 gene regulatory sequences, which results in premature expression of F3/contactin in granule cells. These animals (TAG/F3 mice) display a developmentally regulated cerebellar phenotype in which the size of the cerebellum is markedly reduced during the first two postnatal weeks but subsequently recovers. This is due in part to a reduction in the number of granule cells, most evident in the external germinal layer at postnatal day 3 and in the inner granular layer between postnatal days 8 and 11. The reduction in granule cell number is accompanied by a decrease in precursor granule cell proliferation at postnatal day 3, followed by an increase in the number of cycling cells at postnatal day 8. In the same developmental window the size of the molecular layer is markedly reduced and Purkinje cell dendrites fail to elaborate normally. These data are consistent with a model in which deployment of F3/contactin on granule cells affects proliferation and differentiation of these neurons as well as the differentiation of their synaptic partners, the Purkinje cells. Together, these findings indicate that precise spatio-temporal regulation of TAG-1 and F3/contactin expression is critical for normal cerebellar morphogenesis.
authors.affiliation: Dipartimento di Farmacologia e Fisiologia Umana, Università di Torino, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Bizzoca
authors.forename: Daniela
authors.initials: D
authors.lastname: Virgintino
authors.forename: Loredana
authors.initials: L
authors.lastname: Lorusso
authors.forename: Maura
authors.initials: M
authors.lastname: Buttiglione
authors.forename: Lynn
authors.initials: L
authors.lastname: Yoshida
authors.forename: Angela
authors.initials: A
authors.lastname: Polizzi
authors.forename: Maria
authors.initials: M
authors.lastname: Tattoli
authors.forename: Raffaele
authors.initials: R
authors.lastname: Cagiano
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Rossi
authors.forename: Serguei
authors.initials: S
authors.lastname: Kozlov
authors.forename: Andrew
authors.initials: A
authors.lastname: Furley
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Gennarini
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D002531:Cerebellum / Q000002:abnormalities / Q000166:cytology / Q000254:growth & development*; D002540:Cerebral Cortex / Q000002:abnormalities / Q000166:cytology / Q000254:growth & development; D058967:Contactin 1; D058969:Contactin 2; D058966:Contactins; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008938:Mitosis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011689:Purkinje Cells / Q000473:pathology
chemical_list: C548669:CNTN1 protein, human; C548674:CNTN2 protein, human; D015816:Cell Adhesion Molecules, Neuronal; C548670:Cntn1 protein, mouse; C548675:Cntn2 protein, mouse; D058967:Contactin 1; D058969:Contactin 2; D058966:Contactins