C3orf70 Is Involved in Neural and Neurobehavioral Development

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 <i>C3orf70</i> as a novel common target gene of Neurog1/2 and Ascl1 during neurogenesis. Using in situ hybridization, we demonstrated that <i>c3orf70a</i> and <i>c3orf70b</i>, two orthologs of <i>C3orf70</i>, were expressed in the midbrain and hindbrain of zebrafish larvae. We generated <i>c3orf70</i> knockout zebrafish using CRISPR/Cas9 technology and demonstrated that loss of <i>c3orf70</i> resulted in significantly decreased expression of the mature neuron markers <i>elavl3</i> and <i>eno2</i>. We also found that expression of <i>irx3b</i>, a zebrafish ortholog of <i>IRX3</i> and a midbrain/hindbrain marker, was significantly reduced in <i>c3orf70</i> knockout zebrafish. Finally, we demonstrated that neurobehaviors related to circadian rhythm and altered light&#8722;dark conditions were significantly impaired in <i>c3orf70</i> 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.

Abstract licence: CC BY

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