SummaryMicroRNAs are important players in stem cell biology. Among them, microRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain. Whether miR-9 plays a role in neural stem cell self-renewal and differentiation is unknown. We showed previously that nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector lacking the miR-9 recognition site rescued miR-9-induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses miR-9 pri-miRNA expression. MiR-9, by forming a negative regulatory loop with TLX, establishes a model for controlling the balance between neural stem cell proliferation and differentiation.

Neural stem cell self-renewal and differentiation is orchestrated by precise control of gene expression involving nuclear receptor TLX. Let-7b, a member of the let-7 microRNA family, is expressed in mammalian brains and exhibits increased expression during neural differentiation. However, the role of let-7b in neural stem cell proliferation and differentiation remains unknown. Here we show that let-7b regulates neural stem cell proliferation and differentiation by targeting the stem cell regulator TLX and the cell cycle regulator cyclin D1. Overexpression of let-7b led to reduced neural stem cell proliferation and increased neural differentiation, whereas antisense knockdown of let-7b resulted in enhanced proliferation of neural stem cells. Moreover, in utero electroporation of let-7b to embryonic mouse brains led to reduced cell cycle progression in neural stem cells. Introducing an expression vector of Tlx or cyclin D1 that lacks the let-7b recognition site rescued let-7b-induced proliferation deficiency, suggesting that both TLX and cyclin D1 are important targets for let-7b-mediated regulation of neural stem cell proliferation. Let-7b, by targeting TLX and cyclin D1, establishes an efficient strategy to control neural stem cell proliferation and differentiation.Neural stem cells are undifferentiated precursors that retain the ability to proliferate and self-renew, and they have the capacity to give rise to both neuronal and glial lineages (1). Although the functional properties of neural stem cells have been studied extensively, molecular mechanisms underlying neural stem cell self-renewal and differentiation are only beginning to be understood. One class of factors thought to be important in this process is microRNAs (miRNAs), which are short, 20-22 nucleotide RNA molecules that are expressed in a tissue-specific and developmentally regulated manner and function as negative regulators of gene expression in a variety of eukaryotes. MiRNAs are involved in numerous cellular processes including development, proliferation, and differentiation (2, 3). Studies based on expression patterns, predicted targets, and overexpression analyses suggest that miRNAs are key regulators in stem cell biology.The lethal-7 (let-7) gene is one of the first two miRNAs discovered in Caenorhabditis elegans (C. elegans), and the first known human miRNA (4, 5). Mature let-7 is highly conserved across species in both sequence and function. It plays an important role in development and cell maturation (6-9). Let-7 is expressed in both embryonic and adult brains (10-13). Recently, increased expression and maturation of let-7 has been observed during neural cell specification (8, 9). Let-7a, one of the members of the let-7 family, has been shown to play a role in neuronal differentiation of embryonic neural progenitors (14), while let-7b has been shown to reduce the self-renewal of aging neural stem cells through targeting the high-mobility group A (HMGA) family member Hmga2 expression (15). TLX (NR2E1) is an orphan nuclear receptor that i...

miR-137 is a brain-enriched microRNA. Its role in neural development remains unknown. Here we show that miR-137 plays an essential role in controlling embryonic neural stem cell fate determination. miR-137 negatively regulates cell proliferation and accelerates neural differentiation of embryonic neural stem cells. In addition, we show that histone demethylase LSD1, a transcriptional co-repressor of nuclear receptor TLX, is a downstream target of miR-137. In utero electroporation of miR-137 in embryonic mouse brains led to premature differentiation and outward migration of the transfected cells. Introducing a LSD1 expression vector lacking the miR-137 recognition site rescued miR-137-induced precocious differentiation. Furthermore, we demonstrate that TLX, an essential regulator of neural stem cell self-renewal, represses the expression of miR-137 by recruiting LSD1 to the genomic regions of miR-137. Thus, miR-137 forms a feedback regulatory loop with TLX and LSD1 to control the dynamics between neural stem cell proliferation and differentiation during neural development.

Crops, as the basic source of essential substances and nutrients, do not always contain sufficient amounts of these essential nutrients to meet dietary requirements. In this review paper, we discussed the effects of fertilization and other agronomic measures on the nutritional quality of cereal, oilseed and protein crops, tuber plants and vegetables. Research indicates that application of N, P, K and S fertilizers generally increases crop yield as well as nutritional quality. For example, fertilizer increased protein concentration in cereals and pulses, oil concentration in oilseed crops, starch concentration in tubers, and concentration of essential amino acids and vitamins in vegetables. However, excessive fertilizer application, especially N fertilizer, can result in undesirable changes such as increases in nitrate, titratable acidity and acid to sugar ratio, while decreasing the concentration of vitamin C, soluble sugar, soluble solids, and Mg and Ca in some crops. Other agronomic measures, such as tillage and crop rotation, organic farming, soil moisture management, and crop breeding and genetic engineering can also have a large effect on food crop quality, though the potential benefits of these measures for improving crop quality has not been fully exploited. Research literature on this subject suggests that more information is needed in order to achieve an increase in the concentration of essential microelements, prevent accumulation of toxic levels of elements such as Cu, Mo, Zn, Ni, Se and nitrate, and other dangerous or toxic substances and elements in crops.

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