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DeltaA/DeltaD regulate multiple and temporally distinct phases of notch signaling during dopaminergic neurogenesis in zebrafish.
J Neurosci. 2010 Dec 08; 30(49):16621-35.JN

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, as olig2 expression in ventral diencephalic dopaminergic precursors is affected in dla/dld mutants. DeltaA/D act upstream of sim1a and otpa during dopaminergic specification. However, despite the fact that both dopaminergic and corticotropin-releasing hormone neurons derive from sim1a- and otpa-expressing precursors, DeltaA/D does not act as a lineage switch between these two neuronal types. Rather, DeltaA/D limits the size of the sim1a- and otpa-expressing precursor pool from which dopaminergic neurons differentiate.

Authors+Show Affiliations

Developmental Biology, Institute Biology I, Faculty of Biology, University of Freiburg, and Freiburg Institute for Advanced Studies, University of Freiburg, D-79104 Freiburg, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21148001

Citation

Mahler, Julia, et al. "DeltaA/DeltaD Regulate Multiple and Temporally Distinct Phases of Notch Signaling During Dopaminergic Neurogenesis in Zebrafish." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 30, no. 49, 2010, pp. 16621-35.
Mahler J, Filippi A, Driever W. DeltaA/DeltaD regulate multiple and temporally distinct phases of notch signaling during dopaminergic neurogenesis in zebrafish. J Neurosci. 2010;30(49):16621-35.
Mahler, J., Filippi, A., & Driever, W. (2010). DeltaA/DeltaD regulate multiple and temporally distinct phases of notch signaling during dopaminergic neurogenesis in zebrafish. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 30(49), 16621-35. https://doi.org/10.1523/JNEUROSCI.4769-10.2010
Mahler J, Filippi A, Driever W. DeltaA/DeltaD Regulate Multiple and Temporally Distinct Phases of Notch Signaling During Dopaminergic Neurogenesis in Zebrafish. J Neurosci. 2010 Dec 8;30(49):16621-35. PubMed PMID: 21148001.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - DeltaA/DeltaD regulate multiple and temporally distinct phases of notch signaling during dopaminergic neurogenesis in zebrafish. AU - Mahler,Julia, AU - Filippi,Alida, AU - Driever,Wolfgang, PY - 2010/12/15/entrez PY - 2010/12/15/pubmed PY - 2011/1/8/medline SP - 16621 EP - 35 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 30 IS - 49 N2 - 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, as olig2 expression in ventral diencephalic dopaminergic precursors is affected in dla/dld mutants. DeltaA/D act upstream of sim1a and otpa during dopaminergic specification. However, despite the fact that both dopaminergic and corticotropin-releasing hormone neurons derive from sim1a- and otpa-expressing precursors, DeltaA/D does not act as a lineage switch between these two neuronal types. Rather, DeltaA/D limits the size of the sim1a- and otpa-expressing precursor pool from which dopaminergic neurons differentiate. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/21148001/DeltaA/DeltaD_regulate_multiple_and_temporally_distinct_phases_of_notch_signaling_during_dopaminergic_neurogenesis_in_zebrafish_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=21148001 DB - PRIME DP - Unbound Medicine ER -