Publication List English

2024/08/06
Validation of a new protocol for a zebrafish MEFL (malformation or embryo-fetal lethality) test method that conforms to the ICH S5 (R3) guideline.

2024/05/21
In vivo assessment of individual and total proteinuria in zebrafish larvae using the solvatochromic compound ZMB741

2021/10/31
Generation of a Transgenic Zebrafish Line for In Vivo Assessment of Hepatic Apoptosis

2021/08/19
Patient-Derived Cancer Xenograft Zebrafish Model (PDXZ) for Drug Discovery Screening and Personalized Medicine

2021/07/09
Quality Control Protocol for Zebrafish Developmental Toxicity Studies

tC3orf70 Is Involved in Neural and Neurobehavioral Development

                     
2019/10/15

Pharmaceuticals 2019, 12(4), 156; https://doi.org/10.3390/ph12040156
Accepted: 15 October 2019

Yoshifumi Ashikawa, Takashi Shiromizu, Koki Miura, Yuka Adachi , Takaaki Matsui, Yasumasa Bessho,Toshio Tanaka and Yuhei Nishimura

Abstract
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.

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Pharmaceuticals