TitleMicroRNAs control neurobehavioral development and function in zebrafish.
Publication TypeJournal Article
Year of Publication2012
AuthorsTal, TL, Franzosa, JA, Tilton, SC, Philbrick, KA, Iwaniec, UT, Turner, RT, Waters, KM, Tanguay, RL
JournalFASEB J
Volume26
Issue4
Pagination1452-61
Date Published2012 Apr
ISSN1530-6860
KeywordsAnimals, Behavior, Animal, Brain, Embryo, Nonmammalian, Ethanol, Gene Expression Profiling, Gene Expression Regulation, Developmental, Gene Knockdown Techniques, Humans, Larva, light, MicroRNAs, Oligonucleotide Array Sequence Analysis, Organogenesis, RNA, Messenger, Zebrafish
Abstract

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 skeletal systems.

DOI10.1096/fj.11-194464
Alternate JournalFASEB J.
PubMed ID22253472
PubMed Central IDPMC3316906
Grant ListES00210 / ES / NIEHS NIH HHS / United States
T32ES7060 / ES / NIEHS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States
T32 ES007060 / ES / NIEHS NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States