Specification of hypothalamic neurons by dual regulation of the homeodomain protein Orthopedia
| Autor: | Janna Blechman, Mark Eisenberg, Helit Nabel-Rosen, Gil Levkowitz, Nataliya Borodovsky, Jan Grimm |
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| Přispěvatelé: | University of Zurich, Levkowitz, G |
| Rok vydání: | 2007 |
| Předmět: |
Cell type
Dopamine Models Neurological Hypothalamus 610 Medicine & health Biology medicine.disease_cause Bioinformatics Oxytocin Oligodeoxyribonucleotides Antisense 1309 Developmental Biology 1312 Molecular Biology medicine Animals Receptor Molecular Biology Zebrafish Transcription factor DNA Primers Homeodomain Proteins Neurons Mutation Base Sequence Dopaminergic Gene Expression Regulation Developmental 11359 Institute for Regenerative Medicine (IREM) Zebrafish Proteins biology.organism_classification Homeobox Receptors Vasoactive Intestinal Peptide Signal transduction Carrier Proteins Neuroscience Developmental Biology Receptors Pituitary Adenylate Cyclase-Activating Polypeptide Type I Signal Transduction Transcription Factors |
| Zdroj: | Development (Cambridge, England). 134(24) |
| ISSN: | 0950-1991 |
| Popis: | In the developing hypothalamus, a variety of neurons are generated adjacent to each other in a highly coordinated, but poorly understood process. A critical question that remains unanswered is how coordinated development of multiple neuronal types is achieved in this relatively narrow anatomical region. We focus on dopaminergic (DA) and oxytocinergic (OT) neurons as a paradigm for development of two prominent hypothalamic cell types. We report that the development of DA and OT-like neurons in the zebrafish is orchestrated by two novel pathways that regulate the expression of the homeodomain-containing protein Orthopedia (Otp), a key determinant of hypothalamic neural differentiation. Genetic analysis showed that the G-protein-coupled receptor PAC1 and the zinc finger-containing transcription factor Fezl act upstream to Otp. In vivo and in vitro experiments demonstrated that Fezl and PAC1 regulate Otp at the transcriptional and the post-transcriptional levels, respectively. Our data reveal a new genetic network controlling the specification of hypothalamic neurons in vertebrates,and places Otp as a critical determinant underlying Fezl- and PAC1-mediated differentiation. |
| Databáze: | OpenAIRE |
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