Kapd Is Essential for Specification of the Dopaminergic Neurogenesis in Zebrafish Embryos

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 (Kelch-containing protein associated with PD). Biological functions of were systematically investigated in the zebrafish embryos. First, transcripts of a zebrafish homologue of , 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 caused developmental defects of DA progenitors in the midbrain neural keel and midbrain? hindbrain boundary at 10 hpf. Third, overexpression of increased transcripts level of the dopaminergic immature neuron marker, in the prethalamus at 16.5 hpf. Finally, developmental consequences of knockdown reduced transcripts level of the markers for the immature and mature DA neurons, and 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.