PUBLICATION
The proneural factors Ascl1a and Ascl1b contribute to the terminal differentiation of dopaminergic GABAergic dual transmitter neurons in zebrafish
- Authors
- Altbürger, C., Rath, M., Wehrle, J., Driever, W.
- ID
- ZDB-PUB-231107-4
- Date
- 2023
- Source
- Developmental Biology 505: 587458-74 (Journal)
- Registered Authors
- Driever, Wolfgang
- Keywords
- Ascl1, Dopaminergic neuron, Neurogenesis, Noradrenergic neuron, Zebrafish
- MeSH Terms
-
- Animals
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Basic Helix-Loop-Helix Transcription Factors/metabolism
- Cell Differentiation/physiology
- Dopamine/metabolism
- GABAergic Neurons/metabolism
- Neurogenesis
- Prosencephalon
- Zebrafish*/metabolism
- Zebrafish Proteins*/metabolism
- PubMed
- 37931393 Full text @ Dev. Biol.
Citation
Altbürger, C., Rath, M., Wehrle, J., Driever, W. (2023) The proneural factors Ascl1a and Ascl1b contribute to the terminal differentiation of dopaminergic GABAergic dual transmitter neurons in zebrafish. Developmental Biology. 505:587458-74.
Abstract
The proneural factor Ascl1 is involved in several steps of neurogenesis, from neural progenitor maintenance to initiation of terminal differentiation and neuronal subtype specification. In neural progenitor cells, Ascl1 initiates the cell-cycle exit of progenitors, and contributes to their differentiation into mainly GABAergic neurons. Several catecholaminergic neuron groups in the forebrain of zebrafish use GABA as co-transmitter, but a potential role of the two paralogues Ascl1a and Ascl1b in their neurogenesis is not understood. Here, we show that ascl1a, ascl1b double mutant embryos develop a significantly reduced number of neurons in all GABAergic and catecholaminergic dual transmitter neuron anatomical clusters in the fore- and hindbrain, while glutamatergic catecholaminergic clusters develop normally. However, none of the affected catecholaminergic cell clusters are lost completely, suggesting an impairment in progenitor pools, or a requirement of Ascl1a/b for differentiation of a subset of neurons in each cluster. Early progenitors which are dlx2a+, fezf2 + or emx2 + are not reduced whereas late progenitors and differentiating neurons marked by the expression of dlx5a, isl1 and arxa are severely reduced in ascl1a, ascl1b double mutant embryos. This suggests that Ascl1a and Ascl1b play only a minor or no role in the maintenance of their progenitor pools, but rather contribute to the initiation of terminal differentiation of GABAergic catecholaminergic neurons.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping