PUBLICATION
Kapd Is Essential for Specification of the Dopaminergic Neurogenesis in Zebrafish Embryos
- Authors
- Jung, J., Kim, E., Rhee, M.
- ID
- ZDB-PUB-210407-72
- Date
- 2021
- Source
- Molecules and cells 44(4): 233-244 (Journal)
- Registered Authors
- Keywords
- FAF1, Kapd (Kelch-containing protein associated with PD), Parkinson’s disease, midbrain dopaminergic neurons, next-generation sequencing
- MeSH Terms
-
- Animals
- Dopaminergic Neurons/cytology
- Dopaminergic Neurons/metabolism
- Dopaminergic Neurons/physiology*
- Gene Regulatory Networks
- Mice
- Neurogenesis/genetics*
- Parkinson Disease/genetics*
- Parkinson Disease/pathology
- Zebrafish/embryology*
- PubMed
- 33820883 Full text @ Mol. Cells
Citation
Jung, J., Kim, E., Rhee, M. (2021) Kapd Is Essential for Specification of the Dopaminergic Neurogenesis in Zebrafish Embryos. Molecules and cells. 44(4):233-244.
Abstract
To define novel networks of Parkinson's disease (PD) pathogenesis, the substantia nigra pars compacta of A53T mice, where a death-promoting protein, FAS-associated factor 1 was ectopically expressed for 2 weeks in the 2-, 4-, 6-, and 8-month-old mice, and was subjected to transcriptomic analysis. Compendia of expression profiles and a hierarchical clustering heat map of differentially expressed genes associated with PD were bioinformatically generated. Transcripts level of a particular gene was fluctuated by 20, 60, and 0.75 fold in the 4-, 6-, and 8-month-old mice compared to the 2 months old. Because the gene contained Kelch domain, it was named as Kapd (Kelch-containing protein associated with PD). Biological functions of Kapd were systematically investigated in the zebrafish embryos. First, transcripts of a zebrafish homologue of Kapd, kapd were found in the floor plate of the neural tube at 10 h post fertilization (hpf), and restricted to the tegmentum, hypothalamus, and cerebellum at 24 hpf. Second, knockdown of kapd caused developmental defects of DA progenitors in the midbrain neural keel and midbrain- hindbrain boundary at 10 hpf. Third, overexpression of kapd increased transcripts level of the dopaminergic immature neuron marker, shha in the prethalamus at 16.5 hpf. Finally, developmental consequences of kapd knockdown reduced transcripts level of the markers for the immature and mature DA neurons, nkx2.2, olig2, otx2b, and th in the ventral diencephalon of the midbrain at 18 hpf. It is thus most probable that Kapd play a key role in the specification of the DA neuronal precursors in zebrafish embryos.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping