Neuropilin1 is a direct downstream target of Nurr1 in the developing brain stem
Autor: | Eliza Joodmardi, Elisabet Hermanson, Maria Bergsland, Thomas Perlmann, Lotta Borgius |
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Rok vydání: | 2006 |
Předmět: |
Growth Cones
Central nervous system Down-Regulation Neovascularization Physiologic In situ hybridization Biology Biochemistry Cell Line Mice Cellular and Molecular Neuroscience Nuclear Receptor Subfamily 4 Group A Member 2 Gene expression medicine Animals Promoter Regions Genetic Mice Knockout Orphan receptor Binding Sites Dopaminergic Gene Expression Regulation Developmental Cell Differentiation Vagus Nerve Neuropilin-1 Up-Regulation DNA-Binding Proteins Dorsal motor nucleus medicine.anatomical_structure Nuclear receptor Female Axon guidance Neuroscience Brain Stem Transcription Factors |
Zdroj: | Journal of Neurochemistry. 97:1403-1411 |
ISSN: | 1471-4159 0022-3042 |
DOI: | 10.1111/j.1471-4159.2006.03829.x |
Popis: | The orphan nuclear receptor Nurr1 is expressed in the developing and adult central nervous system. Previous studies have shown that Nurr1 is essential for the generation of midbrain dopamine neurons. Furthermore, Nurr1 is critical for respiratory functions associated with the brain stem. Very few Nurr1 regulated genes have been identified and it remains unclear how Nurr1 influences the function and development of neurons. To identify novel Nurr1 target genes we have searched for regulated genes in the dopaminergic MN9D cell line. These experiments identified Neuropilin-1 (Nrp1), a receptor protein involved in axon guidance and angiogenesis, as a novel Nurr1 target gene. Nrp1 expression was rapidly up-regulated by Nurr1 in MN9D cells and in situ hybridization analysis showed that Nrp1 was coexpressed with Nurr1 in the brain stem dorsal motor nucleus. Importantly, Nrp1 expression was down-regulated in this area in Nurr1 null mice. Moreover, two functional Nurr1 binding sites were identified in the Nrp1 promoter and Nurr1 was found to be recruited to these sites in MN9D cells, further supporting that Nrp1 is a direct downstream target of Nurr1. Taken together, our findings suggest that Nurr1 might influence the processes of axon guidance and/or angiogenesis via the regulation of Nrp1 expression. |
Databáze: | OpenAIRE |
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