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Open AccessArticle

C3orf70 Is Involved in Neural and Neurobehavioral Development

1
Department of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
2
Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Takayama, Nara 630-0192, Japan
3
Department of Systems Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2019, 12(4), 156; https://doi.org/10.3390/ph12040156
Received: 10 October 2019 / Accepted: 15 October 2019 / Published: 16 October 2019
(This article belongs to the Special Issue Zebrafish as a Powerful Tool for Drug Discovery)
Neurogenesis is the process by which undifferentiated progenitor cells develop into mature and functional neurons. Defects in neurogenesis are associated with neurodevelopmental and neuropsychiatric disorders; therefore, elucidating the molecular mechanisms underlying neurogenesis can advance our understanding of the pathophysiology of these disorders and facilitate the discovery of novel therapeutic targets. In this study, we performed a comparative transcriptomic analysis to identify common targets of the proneural transcription factors Neurog1/2 and Ascl1 during neurogenesis of human and mouse stem cells. We successfully identified C3orf70 as a novel common target gene of Neurog1/2 and Ascl1 during neurogenesis. Using in situ hybridization, we demonstrated that c3orf70a and c3orf70b, two orthologs of C3orf70, were expressed in the midbrain and hindbrain of zebrafish larvae. We generated c3orf70 knockout zebrafish using CRISPR/Cas9 technology and demonstrated that loss of c3orf70 resulted in significantly decreased expression of the mature neuron markers elavl3 and eno2. We also found that expression of irx3b, a zebrafish ortholog of IRX3 and a midbrain/hindbrain marker, was significantly reduced in c3orf70 knockout zebrafish. Finally, we demonstrated that neurobehaviors related to circadian rhythm and altered light–dark conditions were significantly impaired in c3orf70 knockout zebrafish. These results suggest that C3orf70 is involved in neural and neurobehavioral development and that defects in C3orf70 may be associated with midbrain/hindbrain-related neurodevelopmental and neuropsychiatric disorders. View Full-Text
Keywords: neurogenesis; neurobehavior; zebrafish; comparative transcriptome analysis; gene coexpression network neurogenesis; neurobehavior; zebrafish; comparative transcriptome analysis; gene coexpression network
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Ashikawa, Y.; Shiromizu, T.; Miura, K.; Adachi, Y.; Matsui, T.; Bessho, Y.; Tanaka, T.; Nishimura, Y. C3orf70 Is Involved in Neural and Neurobehavioral Development. Pharmaceuticals 2019, 12, 156.

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