Abstract
Exploration of non-coding genome has recently uncovered a growing list of formerly unknown regulatory long non-coding RNAs (lncRNAs) with important functions in stem cell pluripotency, development and homeostasis of several tissues. Although thousands of lncRNAs are expressed in mammalian brain in a highly patterned manner, their roles in brain development have just begun to emerge. Recent data suggest key roles for these molecules in gene regulatory networks controlling neuronal and glial cell differentiation. Analysis of the genomic distribution of genes encoding for lncRNAs indicates a physical association of these regulatory RNAs with transcription factors (TFs) with well-established roles in neural differentiation, suggesting that lncRNAs and TFs may form coherent regulatory networks with important functions in neural stem cells (NSCs). Additionally, many studies show that lncRNAs are involved in the pathophysiology of brain-related diseases/disorders. Here we discuss these observations and investigate the links between lncRNAs, brain development and brain-related diseases. Understanding the functions of lncRNAs in NSCs and brain organogenesis could revolutionize the basic principles of developmental biology and neuroscience.
Highlights
A long standing question in biological sciences is how cell diversity, specification patterns, and tissue complexity are generated during organ development
Subsequent studies using high-throughput transcriptomic data to examine long non-coding RNA (lncRNA) differential expression in neural stem cells (NSCs), GABAergic neurons and oligodendrocytes, led to the identification of lncRNAs that are dynamically regulated during neural lineage specification, neuronal-glia fate switching and oligodendrocyte maturation [i.e., distal-less homeobox 1 antisense (Dlx1AS) (Distal-less homeobox 1 antisense), embryonic ventral forebrain 2 (Evf2) (Embryonic ventral forebrain 2), rhabdomyosarcoma associated transcript (Rmst), utNgn1, MALAT1] (Mercer et al, 2010; Qureshi and Mehler, 2012; Ng et al, 2013)
Specific large intergenic noncoding RNA (lincRNA) appeared to localize near genes encoding key transcription factors (TFs) that are involved in processes ranging from hippocampal development to neuronal and oligodendrocyte maturation (Guttman et al, 2009; Qureshi and Mehler, 2012)
Summary
A long standing question in biological sciences is how cell diversity, specification patterns, and tissue complexity are generated during organ development. Subsequent studies using high-throughput transcriptomic data (microarray platform) to examine lncRNA differential expression in NSCs, GABAergic neurons and oligodendrocytes, led to the identification of lncRNAs that are dynamically regulated during neural lineage specification, neuronal-glia fate switching and oligodendrocyte maturation [i.e., Dlx1AS (Distal-less homeobox 1 antisense), Evf (Embryonic ventral forebrain 2), Rmst, utNgn (untranslated Neurogenin1), MALAT1 (metastasis-associated lung adenocarcinoma transcript 1; named NEAT2)] (Mercer et al, 2010; Qureshi and Mehler, 2012; Ng et al, 2013). ChIP-Seq approaches were developed to generate and investigate genome-wide chromatin-state maps These functional analyses predicted hypothetical roles for 150 mammalian lincRNAs (long intergenic non-coding RNAs) in a “guilt-by-association” manner in NSCs. In particular, specific lincRNAs appeared to localize near genes encoding key TFs (such as Sox, Klf, Myc, p53, NFkB and Brn1) that are involved in processes ranging from hippocampal development to neuronal and oligodendrocyte maturation (Guttman et al, 2009; Qureshi and Mehler, 2012). Microarray data analysis led to the identification of 35 neuronal lncRNAs with important roles in neuronal differentiation, e.g., Rmst (AK056164, AF429305 and AF429306), lncRNA_N1 (AK124684), lncRNA_N2 (AK091713),
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
