Tal, T.L., Franzosa, J.A., Tilton, S.C., Philbrick, K.A., Iwaniec, U.T., Turner, R.T., Waters, K.M., and Tanguay, R.L. (2012) MicroRNAs control neurobehavioral development and function in zebrafish. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 26(4):1452-1461.
microRNAs (miRNAs) have emerged as regulators of a broad spectrum of neurodevelopmental processes, including brain morphogenesis,
neuronal differentiation, and survival. While the role of miRNAs in establishing and maintaining the developing nervous system
is widely appreciated, the developmental neurobehavioral role of miRNAs has yet to be defined. Here we show that transient
disruption of brain morphogenesis by ethanol exposure results in behavioral hyperactivity in larval zebrafish challenged with
changes in lighting conditions. Aberrations in swimming activity persist in juveniles that were developmentally exposed to
ethanol. During early neurogenesis, multiple gene expression profiling studies revealed widespread changes in mRNA and miRNA
abundance in ethanol-exposed embryos. Consistent with a role for miRNAs in neurobehavioral development, target prediction
analyses identified multiple miRNAs misexpressed in the ethanol-exposed cohorts that were also predicted to target inversely
expressed transcripts known to influence brain morphogenesis. In vivo knockdown of miR-9/9* or miR-153c persistently phenocopied the effect of ethanol on larval and juvenile swimming behavior.
Structural analyses performed on adults showed that repression of miR-153c during development impacts craniofacial skeletal
development. Together, these data support an integral role for miRNAs in the establishment of vertebrate neurobehavioral and