Transgenic mice expressing F3/contactin from the TAG-1 promoter exhibit developmentally regulated changes in the differentiation of cerebellar neurons
| Autor: | Serguei Kozlov, Loredana Lorusso, Daniela Virgintino, Lynn Yoshida, Gianfranco Gennarini, Ferdinando Rossi, Antonella Bizzoca, Andrew J.W. Furley, Maria Tattoli, Angela Polizzi, Maura Buttiglione, Raffaele Cagiano |
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| Rok vydání: | 2003 |
| Předmět: |
Genetically modified mouse
Cerebellum Cell Adhesion Molecules Neuronal Purkinje cell Morphogenesis Mitosis Mice Transgenic Granular layer Biology Mice Purkinje Cells Contactin 1 Contactins Contactin 2 medicine Animals Humans Progenitor cell Promoter Regions Genetic Molecular Biology Cells Cultured Cerebral Cortex Neurons Genetics Cell Death Gene Expression Regulation Developmental Cell Differentiation Granule cell Axons Cell biology medicine.anatomical_structure Animals Newborn Cerebellar cortex Cell Division Developmental Biology |
| Zdroj: | Development. 130:29-43 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.00183 |
| Popis: | 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 byTAG-1 gene regulatory sequences, which results in premature expression of F3/contactin in granule cells. These animals (TAG/F3mice) 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. |
| Databáze: | OpenAIRE |
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