PUBLICATION
An ancient neurotrophin receptor code; a single Runx/Cbfβ complex determines somatosensory neuron fate specification in zebrafish
- Authors
- Gau, P., Curtright, A., Condon, L., Raible, D.W., Dhaka, A.
- ID
- ZDB-PUB-170715-2
- Date
- 2017
- Source
- PLoS Genetics 13: e1006884 (Journal)
- Registered Authors
- Raible, David
- Keywords
- Neurons, Zebrafish, Embryos, Nociceptors, Vertebrates, Ganglia, Gene expression, In situ hybridization
- MeSH Terms
-
- Animals
- Cell Differentiation
- Core Binding Factor Alpha 3 Subunit/genetics
- Core Binding Factor Alpha 3 Subunit/metabolism*
- Core Binding Factor beta Subunit/genetics
- Core Binding Factor beta Subunit/metabolism*
- Gene Expression Regulation, Developmental
- Larva/genetics
- Larva/metabolism
- Neurogenesis/genetics*
- Neurons/metabolism
- Promoter Regions, Genetic
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Receptors, Nerve Growth Factor/genetics
- Receptors, Nerve Growth Factor/metabolism*
- Sensory Receptor Cells/metabolism
- Sequence Alignment
- Sequence Analysis, DNA
- Signal Transduction
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 28708822 Full text @ PLoS Genet.
Citation
Gau, P., Curtright, A., Condon, L., Raible, D.W., Dhaka, A. (2017) An ancient neurotrophin receptor code; a single Runx/Cbfβ complex determines somatosensory neuron fate specification in zebrafish. PLoS Genetics. 13:e1006884.
Abstract
In terrestrial vertebrates such as birds and mammals, neurotrophin receptor expression is considered fundamental for the specification of distinct somatosensory neuron types where Traka, TrkB and TrkC specify nociceptors, mechanoceptors and proprioceptors/mechanoceptors, respectively. In turn, Runx transcription factors promote neuronal fate specification by regulating neurotrophin receptor and sensory receptor expression where Runx1 mediates TrkA+ nociceptor diversification while Runx3 promotes a TrkC+ proprioceptive/mechanoceptive fate. Here, we report in zebrafish larvae that orthologs of the neurotrophin receptors in contrast to terrestrial vertebrates mark overlapping and distinct subsets of nociceptors suggesting that TrkA, TrkB and TrkC do not intrinsically promote nociceptor, mechanoceptor and proprioceptor/mechanoceptor neuronal fates, respectively. While we find that zebrafish Runx3 regulates nociceptors in contrast to terrestrial vertebrates, it shares a conserved regulatory mechanism found in terrestrial vertebrate proprioceptors/mechanoceptors in which it promotes TrkC expression and suppresses TrkB expression. We find that Cbfβ, which enhances Runx protein stability and affinity for DNA, serves as an obligate cofactor for Runx in neuronal fate determination. High levels of Runx can compensate for the loss of Cbfβ, indicating that in this context Cbfβ serves solely as a signal amplifier of Runx activity. Our data suggests an alteration/expansion of the neurotrophin receptor code of sensory neurons between larval teleost fish and terrestrial vertebrates, while the essential roles of Runx/Cbfβ in sensory neuron cell fate determination while also expanded are conserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping