DLX6-AS1

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DLX6-AS1: a brain-regulating long non-coding RNA

DLX6-AS1, also known as Evf-1, is a developmentally regulated long non-coding RNA. It helps control brain development rather than coding a protein. In rats, DLX6-AS1 is active in neurons of the developing forebrain’s subventricular zone, and its expression is linked to Sonic hedgehog (Shh) signaling and the DLX gene family, both important for ventral forebrain and craniofacial development.

A related, alternatively spliced form called DLX6-AS2 (Evf-2) can bind the Dlx-2 protein to form a complex that increases the activity of the Dlx5 and Dlx6 genes. DLX6-AS2 helps regulate gene expression in the brain region that produces GABAergic interneurons during development and works with DLX homeodomain proteins to boost the DLX5/6 enhancer in neural stem cells. These interneurons end up in the hippocampus of the adult brain, a region tied to learning and memory.

GABAergic interneurons are thought to play a role in several psychiatric disorders, including autism, schizophrenia, and epilepsy. Because DLX6-AS2 controls the development of these neurons, it has been studied for possible links to these conditions.

DLX6-AS2 is notable for being the first known long non-coding RNA involved in organogenesis, the process of organ development.

See also: long noncoding RNA, Dlx genes, gamma-aminobutyric acid (GABA), chemoaffinity hypothesis.