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Journal of Neuroscience
Article . 2010 . Peer-reviewed
License: CC BY NC SA
Data sources: Crossref
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DeltaA/DeltaD Regulate Multiple and Temporally Distinct Phases of Notch Signaling during Dopaminergic Neurogenesis in Zebrafish

Authors: Mahler, Julia; Filippi, Alida; Driever, Wolfgang;

DeltaA/DeltaD Regulate Multiple and Temporally Distinct Phases of Notch Signaling during Dopaminergic Neurogenesis in Zebrafish

Abstract

Dopaminergic neurons develop at distinct anatomical sites to form some of the major neuromodulatory systems in the vertebrate brain. Despite their relevance in neurodegenerative diseases and the interests in reconstitutive therapies from stem cells, mechanisms of the neurogenic switch from precursor populations to dopaminergic neurons are not well understood. Here, we investigated neurogenesis of different dopaminergic and noradrenergic neuron populations in the zebrafish embryo. Birth-dating analysis by EdU (5-ethynyl-2′-deoxyuridine) incorporation revealed temporal dynamics of catecholaminergic neurogenesis. Analysis of Notch signaling mutants and stage-specific pharmacological inhibition of Notch processing revealed that dopaminergic neurons form by temporally distinct mechanisms: dopaminergic neurons of the posterior tuberculum derive directly from neural plate cells during primary neurogenesis, whereas other dopaminergic groups form in continuous or wavelike neurogenesis phases from proliferating precursor pools. Systematic analysis of Notch ligands revealed that the two zebrafish co-orthologs of mammalian Delta1, DeltaA and DeltaD, control the neurogenic switch of all early developing dopaminergic neurons in a partially redundant manner. DeltaA/D may also be involved in maintenance of dopaminergic precursor pools, asolig2expression in ventral diencephalic dopaminergic precursors is affected indla/dldmutants. DeltaA/D act upstream ofsim1aandotpaduring dopaminergic specification. However, despite the fact that both dopaminergic and corticotropin-releasing hormone neurons derive fromsim1a- andotpa-expressing precursors, DeltaA/D does not act as a lineage switch between these two neuronal types. Rather, DeltaA/D limits the size of thesim1a- andotpa-expressing precursor pool from which dopaminergic neurons differentiate.

Country
Germany
Related Organizations
Keywords

Embryo, Nonmammalian, Receptors, Notch, Corticotropin-Releasing Hormone, Dopamine, Neurogenesis, Cell Cycle, Intracellular Signaling Peptides and Proteins, Brain, Gene Expression Regulation, Developmental, Membrane Proteins, Nerve Tissue Proteins, Dipeptides, Deoxyuridine, Oligodeoxyribonucleotides, Antisense, Animals, Genetically Modified, Mutation, Basic Helix-Loop-Helix Transcription Factors, Animals, HSP70 Heat-Shock Proteins, Enzyme Inhibitors

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    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
49
Top 10%
Top 10%
Top 10%
hybrid