C3orf70 is associated with neural and neurobehavioral development

Abstract

Neurogenesis is the process by which undifferentiated progenitor cells convert into mature and functional neurons. Impairments in neurogenesis are associated with neurodevelopmental and neuropsychiatric disorders. Elucidating the molecular mechanisms underlying neurogenesis can stimulate further understanding of the pathophysiology and the discovery of novel therapeutic targets for these disorders. In this study, we performed a comparative transcriptomic analysis to reveal common targets of the proneural transcription factors, Neurog1/2 or Ascl1, during neurogenesis of human and mouse stem cells. We successfully identified C3orf70 as a novel common target of Neurog1/2 and Ascl1 during neurogenesis. Two orthologs of C3orf70 were expressed in the midbrain and hindbrain of zebrafish larvae. We generated c3orf70 knockout zebrafish using CRISPR/Cas9. The expression of the mature neuron markers elavl3 and eno2 was significantly decreased in c3orf70 knockout zebrafish. The expression of irx3b, a zebrafish ortholog of IRX3 and a midbrain/hindbrain marker, was significantly reduced in c3orf70 knockout zebrafish. Neurobehaviors related to circadian rhythm and changing light-dark conditions were significantly impaired in c3orf70 knockout zebrafish. These results suggested that C3orf70 is involved in neural and neurobehavioral development. Defects in C3orf70 may be associated with midbrain/hindbrain-related neurodevelopmental and neuropsychiatric disorders. Poster Sessions