title: The gene encoding the mouse contactin-1 axonal glycoprotein is regulated by the collier/Olf1/EBF family early B-Cell factor 2 transcription factor.
abstract: The Contactin-1 axonal glycoprotein (formerly F3/Contactin) plays a relevant role in cerebellar ontogenesis, as shown in Contactin-1 KO-mice and in transgenic mice misexpressing the corresponding cDNA from a heterologous promoter. Likewise, null mutant mice for the Collier/Olf1/Early B-cell family transcription factor EBF2, in which Purkinje neuron development is primarily affected, exhibit abnormalities in cerebellar corticogenesis. Here, to evaluate the contribution to the Ebf2 null phenotype of changes in the profile of Contactin-1, we study its expression in Ebf2 null mice. In addition, we explore the activation profile of the Cntn1 gene promoter upon transferring the Ebf2 mutation to transgenic mice expressing an enhanced green fluorescent protein reporter under control of Cntn1 gene regulatory sequences. In Ebf2 null mice, Contactin-1 protein expression and Cntn1 gene promoter activity are both downregulated during embryonic and early postnatal cerebellar development, both in the rostral and caudal folia, while in the latter an upregulation is observed at postnatal day 8. In vitro, vectors driving EBF1,2,3 transcription factors from a cytomegalovirus (CMV) promoter transactivate a Cntn1-Choline acetyltransferse (CAT) promoter-reporter construct in cotransfection assays and, accordingly, by chromatin immunoprecipitation, we show that the Cntn1 gene 5' flanking region is bound by the EBF2 transcription factor, consistent with the evidence that this region bears the cognate deoxyribonucleic acid (DNA) consensus sequences. These data indicate that Contactin-1 expression is dependent upon EBF factors, suggesting that the Cntn1 gene belongs to the expanding regulatory cascade driven by these transcriptional regulators so that changes in its activation may contribute to the phenotype of Ebf2 null mutant mice.
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Medical School, University of Bari, Policlinico, Bari, I-70124, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Bizzoca
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Medical School, University of Bari, Policlinico, Bari, I-70124, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Picocci
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Medical School, University of Bari, Policlinico, Bari, I-70124, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Corsi
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Medical School, University of Bari, Policlinico, Bari, I-70124, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Arbia
authors.affiliation: Division of Neuroscience, San Raffaele Scientific Institute, Milano, I-20132, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Croci
authors.affiliation: Division of Neuroscience, San Raffaele Scientific Institute, Milano, I-20132, Italy.|Università Vita-Salute San Raffaele, Milano, I-20132, Italy.
authors.forename: G Giacomo
authors.initials: GG
authors.lastname: Consalez
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Medical School, University of Bari, Policlinico, Bari, I-70124, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Gennarini
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D058967:Contactin 1 / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002795:Choline O-Acetyltransferase; D058967:Contactin 1; D049452:Green Fluorescent Proteins; D015534:Trans-Activators; C548670:Cntn1 protein, mouse; C489921:Ebf1 protein, mouse; C489922:Ebf2 protein, mouse; C485184:enhanced green fluorescent protein
keywords: Contactin-1; EBF factors; cell-cell interactions; cerebellar development; gene regulation