Role of , GABA receptor alpha-2 subunit, in CNS development.

gene codes for the alpha-2 subunit of the GABA receptor, one of the ionotropic receptors which has been related to anxiety, depression and other behavioural disorders, including drug dependence and schizophrenia. GABAergic signalling also plays a role during development, by promoting neural stem cell maintenance and renewal. To investigate the role of in CNS development, deficient zebrafish were generated. The pattern of proliferation during the embryonic development was disrupted in morphant embryos, which also displayed an increase in the number of apoptotic nuclei mainly at the mid- and hindbrain regions. The expression of several genes ( and ) known to contribute to the development of the central nervous system was also affected in morpholino-injected embryos, although no changes were found for and expression. The transcriptional activity of (a proneural gene involved in early neuronal determination) was down-regulated in deficient embryos, and the expression pattern of (GABA-synthesising enzyme GAD67) was clearly reduced in injected fish. I propose that might be interacting with those signalling pathways that regulate proliferation, differentiation and neurogenesis during the embryonic development; thus, might be playing a role in the differentiation of the mesencephalon and cerebellum. Given that changes in GABAergic circuits during development have been related to several psychiatric disorders, such as autism and schizophrenia, this work might be helpful to understand the role of neurotransmitter systems during CNS development and to assess the developmental effects of several GABAergic drugs.