Foxa1andFoxa2regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner
| Autor: | Siew-Lan Ang, Yannis E. Mavromatakis, Jeffrey A. Whitsett, Anna L M Ferri, Hiroshi Sasaki, Julie C. Wang, Wei Lin |
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| Rok vydání: | 2007 |
| Předmět: |
Hepatocyte Nuclear Factor 3-alpha
Male medicine.medical_specialty Dopamine Gene Dosage Mice Transgenic Nerve Tissue Proteins Biology Models Biological Midbrain Mice Mesencephalon Pregnancy Internal medicine Basic Helix-Loop-Helix Transcription Factors medicine Animals Molecular Biology Transcription factor reproductive and urinary physiology Homeodomain Proteins Neurons Regulation of gene expression Tyrosine hydroxylase Stem Cells Neurogenesis Dopaminergic Gene Expression Regulation Developmental Cell Differentiation Zebrafish Proteins respiratory system Cell biology Homeobox Protein Nkx-2.2 Endocrinology nervous system embryonic structures Hepatocyte Nuclear Factor 3-beta Female FOXA2 FOXA1 Transcription Factors Developmental Biology |
| Zdroj: | Development. 134:2761-2769 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.000141 |
| Popis: | The role of transcription factors in regulating the development of midbrain dopaminergic (mDA) neurons is intensively studied owing to the involvement of these neurons in diverse neurological disorders. Here we demonstrate novel roles for the forkhead/winged helix transcription factors Foxa1 and Foxa2 in the specification and differentiation of mDA neurons by analysing the phenotype of Foxa1 and Foxa2 single- and double-mutant mouse embryos. During specification, Foxa1 and Foxa2 regulate the extent of neurogenesis in mDA progenitors by positively regulating Ngn2 (Neurog2)expression. Subsequently, Foxa1 and Foxa2 regulate the expression of Nurr1(Nr4a2) and engrailed 1 in immature neurons and the expression of aromatic l-amino acid decarboxylase and tyrosine hydroxylase in mature neurons during early and late differentiation of midbrain dopaminergic neurons. Interestingly, genetic evidence indicates that these functions require different gene dosages of Foxa1 and Foxa2. Altogether, our results demonstrate that Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner. |
| Databáze: | OpenAIRE |
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