DLX6-AS1 explained

DLX6 antisense RNA 1 (DLX6-AS1) (Evf-1 (Embryonic ventral forebrain-1)) is a developmentally-regulated long non-coding RNA. In rats, it is expressed in neurons in the subventricular zone of the developing forebrain. Its expression is linked to that of the Shh (sonic hedgehog) and DLX families of genes, which are important in ventral forebrain and craniofacial development.^[1] An alternatively spliced form of DLX6-AS1, DLX6-AS2, forms a stable complex with the Dlx-2 protein. This complex activates transcription of Dlx-5 and Dlx-6.^[2]

DLX6-AS2 regulates gene expression in a region of the brain which produces GABAergic interneurons during development.^[3] It is involved in the signaling pathway and works in conjunction with DLX homeodomain proteins to increase the effectiveness of the Dlx5/6 enhancer element within neural stem cells. The interneurons are found in the hippocampus of the adult brain, an area responsible for learning and memory.^[4]

GABAergic interneurons have been implicated in a number of psychiatric disorders including autism,^[5] schizophrenia^[6] and epilepsy;^[7] as DLX6-AS2 controls the development of these neurons, it has been subject to studies regarding the causation of these disorders.

DLX6-AS2 is the first known long non-coding RNA to be involved in organogenesis.^[8]

See also

• Long noncoding RNA
• Dlx (gene)
• Gamma-Aminobutyric acid
• Chemoaffinity hypothesis

Further reading

• Kohtz JD, Baker DP, Corte G, Fishell G . Regionalization within the mammalian telencephalon is mediated by changes in responsiveness to Sonic Hedgehog . Development . 125 . 24 . 5079–5089 . December 1998 . 10.1242/dev.125.24.5079 . 9811591 . 2010-07-26.
• Ingham PW, McMahon AP . Hedgehog signaling in animal development: paradigms and principles . Genes Dev. . 15 . 23 . 3059–3087 . December 2001 . 11731473 . 10.1101/gad.938601 . free .
• Licastro D, Gennarino VA, Petrera F, Sanges R, Banfi S, Stupka E . Promiscuity of enhancer, coding and non-coding transcription functions in ultraconserved elements . BMC Genomics . 11 . 151 . 2010 . 20202189 . 2847969 . 10.1186/1471-2164-11-151 . free .
• Erdmann VA, Barciszewska MZ, Hochberg A, de Groot N, Barciszewski J . Regulatory RNAs . Cell. Mol. Life Sci. . 58 . 7 . 960–977 . June 2001 . 11497242 . 10.1007/PL00000913. 19491637 . 11337372 .

Notes and References

1. Kohtz JD, Fishell G . Developmental regulation of EVF-1, a novel non-coding RNA transcribed upstream of the mouse Dlx6 gene . Gene Expr. Patterns . 4 . 4 . 407–412 . July 2004 . 15183307 . 10.1016/j.modgep.2004.01.007 .
2. Feng J, Bi C, Clark BS, Mady R, Shah P, Kohtz JD . The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator . Genes Dev. . 20 . 11 . 1470–1484 . June 2006 . 16705037 . 1475760 . 10.1101/gad.1416106 .
3. Web site: Non-Coding RNA Called Evf2 Is Important For Gene Regulation. Sep 1, 2009. Sciencedaily. 26 July 2010.
4. Bond AM, Vangompel MJ, Sametsky EA . Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry . Nat. Neurosci. . 12 . 8 . 1020–1027 . August 2009 . 19620975 . 10.1038/nn.2371 . 3203213. etal.
5. Dani VS, Chang Q, Maffei A, Turrigiano GG, Jaenisch R, Nelson SB . Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett syndrome . Proc. Natl. Acad. Sci. U.S.A. . 102 . 35 . 12560–12565 . August 2005 . 16116096 . 1194957 . 10.1073/pnas.0506071102 . 2005PNAS..10212560D . free .
6. Lewis DA, Hashimoto T, Volk DW . Cortical inhibitory neurons and schizophrenia . Nat. Rev. Neurosci. . 6 . 4 . 312–324 . April 2005 . 15803162 . 10.1038/nrn1648 . 3335493 .
7. Di Cristo G . Development of cortical GABAergic circuits and its implications for neurodevelopmental disorders . Clin. Genet. . 72 . 1 . 1–8 . July 2007 . 17594392 . 10.1111/j.1399-0004.2007.00822.x . 22162349 .
8. Shamovsky I, Nudler E . Gene control by large noncoding RNAs . Sci. STKE . 2006 . 355 . pe40 . October 2006 . 17018852 . 10.1126/stke.3552006pe40 . 41151259 .