Summary: Neural tube defects (NTDs) are the second most common birth defects in the United States. It is well known that folic acid supplementation decreases about 70% of all NTDs, although the mechanism by which this occurs is still relatively unknown. The current theory is that folic acid deficiency ultimately leads to depletion of the methyl pool, leaving critical genes unmethylated, and, in turn, their improper expression leads to failure of normal neural tube development. Recently, new studies in human cell lines have shown that folic acid deficiency and DNA hypomethylation can lead to misexpression of microRNAs (miRNAs). Misexpression of critical miRNAs during neural development may lead to a subtle effect on neural gene regulation, causing the sometimes mild to severely debilitating range of phenotypes exhibited in NTDs. This review seeks to cohesively integrate current information regarding folic acid deficiency, methylation cycles, neural development, and miRNAs to propose a potential model of NTD formation. In addition, we have examined the relevant gene pathways and miRNAs that are predicted to affect them, and based on our investigation, we have devised a basic template of experiments for exploring the idea that miRNA misregulation may be linked to folic acid deficiency and NTDs. genesis 48:282-294, 2010. V V C 2010 Wiley-Liss, Inc.
Since their discovery nearly two decades ago, microRNAs (miRNAs) have been found in a variety of organisms including plants, fish, and mammals and been shown to have an enormous impact on development and disease. This chapter provides a comprehensive overview of the biogenesis of miRNAs, their mechanisms of action, and their specific role in regulating self-renewal and lineage specification of embryonic and adult stem cells. In the latter case, emphasis is placed on the miRNA regulatory networks that mediate cellular differentiation. Their role in regulating cellular responses to stress and in various neurologic diseases, autoimmunity, and cancer are also described. Finally, a brief overview of methods used to analyze the function of miRNAs and identify their targets in vivo is provided.
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