Mir-9

MINI REVIEW ARTICLE
published: 16 May 2012 doi: 10.3389/fgene.2012.00077

MicroRNAs and fetal brain development: implications for ethanol teratology during the second trimester period of neurogenesis
Rajesh C. Miranda*
Texas A&M Health Science Center, Bryan, USA

Edited by: Matthew Reilly, National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism, USA Reviewed by:Peter G. Clote, Boston College, USA Ricardo Silva, Universidad Simón Bolívar, Venezuela *Correspondence: Rajesh C. Miranda, Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M Health Science Center, Medical Research and Education Building, 8447 State Highway 47 , Bryan, TX 77807-3260, USA e-mail: miranda@medicine. tamhsc.edu

Maternal ethanol consumption duringpregnancy can lead to a stereotypic cluster of fetal craniofacial, cardiovascular, skeletal, and neurological deficits that are collectively termed the fetal alcohol spectrum disorder (FASD). Fetal ethanol exposure is a leading non-genetic cause of mental retardation. Mechanisms underlying the etiology of ethanol teratology are varied and complex. This review will focus on the developing brain asan important and vulnerable ethanol target. Near the end of the first trimester, and during the second trimester, fetal neural stem cells (NSCs) produce most of the neurons of the adult brain, and ethanol has been shown to influence NSC renewal and maturation. We will discuss the neural developmental and teratological implications of the biogenesis and function of microRNAs (miRNAs), a class ofsmall non-protein-coding RNAs that control the expression of gene networks by translation repression. A small but growing body of research has identified ethanol-sensitive miRNAs at different stages of NSC and brain maturation. While many miRNAs appear to be vulnerable to ethanol at specific developmental stages, a few, like the miR-9 family, appear to exhibit broad vulnerability to ethanol acrossmultiple stages of NSC differentiation. An assessment of the regulation and function of these miRNAs provides important clues about the mechanisms that underlie fetal vulnerability to alterations in the maternal-fetal environment and yields insights into the genesis of FASD.
Keywords: microRNA, fetal alcohol spectrum disorders, FASD, miR-9, neural stem cells, cerebral cortical development

Heavyethanol exposure during pregnancy can lead to fetal growth retardation, and to a constellation of craniofacial, cardiovascular, skeletal, and brain growth defects (Clarren et al., 1978; Clarren, 1986) that are collectively termed “Fetal Alcohol Spectrum Disorder” (FASD; Lemoine et al., 1968; Jones et al., 1973). Brain defects can include, microencephaly, the loss of the corpus callosum, and theemergence of heterotopias. FASD is a leading, non-genetic cause of mental retardation. Epidemiological studies (SAMHSA, 2009) show that 6.8% of pregnant women report continued ethanol consumption into the third trimester of pregnancy. Moreover, 2–5% of school-aged children in the US are estimated to exhibit symptoms associated with fetal ethanol exposure (May et al., 2009). Importantly, nutrition(Thomas et al., 2009; Keen et al., 2010), and drugs of abuse like nicotine (Chen et al., 1998, 1999) also contextually enhance or mitigate effects of prenatal ethanol exposure. It is important to understand the genesis of fetal vulnerability to disrupters of the maternal-fetal environment.

early perturbations in the maternal-fetal environment, so that relatively minor disruptions in genetic andepigenetic instructions that guide stem cell maturation will significantly alter the structure and function of the mature brain.
CEREBRAL CORTICAL NEUROGENESIS, AN EXAMPLE OF ETHANOL VULNERABILITY

NEURAL STEM CELLS AND NEUROGENESIS; SECOND TRIMESTER BRAIN VULNERABILITY The gestational period spanning the end of the first trimester through the second trimester of fetal development is a specific...