Abstract
Dysfunctions in the GABAergic system lead to various pathological conditions and impaired inhibitory function is one of the causes behind neuropathies characterized by neuronal hyper excitability. The Dlx homeobox genes are involved in the development of nervous system, neural crest, branchial arches and developing appendages. Dlx genes also take part in neuronal migration and differentiation during development, more precisely, in the migration and differentiation of GABAergic neurons. Functional analysis of dlx genes has mainly been carried out in developing zebrafish embryos and larvae, however information regarding the expression and roles of these genes in the adult zebrafish brain is still lacking. The extensive neurogenesis that takes place in the adult zebrafish brain, makes them a good model for the visualization of mechanisms involving dlx genes during adulthood in physiological conditions and during regeneration of the nervous system. We have identified the adult brain regions where transcripts of dlx1a, dlx2a, dlx5a and dlx6a genes are normally found and have confirmed that within telencephalic domains, there is high overlapping expression of the four dlx paralogs with a marker for GABAergic neurons. Co-localization analyses carried with the Tg(dlx6a-1.4kbdlx5a/dlx6a:GFP) reporter line have also shown that in some areas of the diencephalon, cells expressing the dlx5a/6a bigene may have a neural stem cell identity. Furthermore, investigations in a response to stab wound lesions, have demonstrated a possible participation of the dlx5a/6a bigene, most likely of dlx5a, during regeneration of the adult zebrafish brain. These observations suggest a possible participation of dlx-expressing cells during brain regeneration in adult zebrafish and also provide information on the role of dlx genes under normal physiological conditions in adults.
Highlights
The transcription factors encoded by Dlx genes play key roles in the patterning of the vertebrate limb and the central nervous system (CNS) [1], Dlx genes are required in the development of the mammalian brain [2]
We report the expression of dlx genes in the adult zebrafish brain, characterize the GABAergic and neural stem cells (NSCs) identity of cells expressing dlx in adults, and the changes in expression of these genes, of dlx5a and dlx5a/6a, during regeneration in a post-injury response
Transcripts of dlx2a and dlx5a were observed within the central nucleus of the ventral telencephalic area (Vc)
Summary
The transcription factors encoded by Dlx genes play key roles in the patterning of the vertebrate limb and the central nervous system (CNS) [1], Dlx genes are required in the development of the mammalian brain [2] These genes are required for correct migration and differentiation of progenitors that will later give rise to GABAergic interneurons [1,3]. The deletion of one of these regions in mice, I56ii, has been shown to impair the expression of Dlx genes and of potential targets including Gad and other striatal markers [11] The identification of such regulatory elements was a starting point for the generation of the Tg(dlx6a-1.4kbdlx5a/dlx6a:GFP) reporter line that mimics the endogenous expression patterns of dlx5a/dlx6a genes in the forebrain [10,12]. During a regeneration response following stab injury, we observed a down-regulation followed by up-regulation of the dlx5a paralog in different time points and up-regulation of the dlx5a/6a bigene
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