Activity of dlx5a/dlx6a regulatory elements during zebrafish GABAergic neuron development
- 31 October 2011
- journal article
- research article
- Published by Wiley in International Journal of Developmental Neuroscience
- Vol. 29 (7), 681-691
- https://doi.org/10.1016/j.ijdevneu.2011.06.005
Abstract
During vertebrate forebrain formation, Dlx homeobox genes play essential roles in the differentiation, migration and survival of subpallial precursor cells that will later give rise to diverse subtypes of gamma-aminobutyric acid (GABA)-expressing neurons, including inhibitory cortical interneurons in mammals. They also participate in the regulation of the Gad genes encoding the enzymes necessary for GABA synthesis. In mice, at least four cis-regulatory elements (CREs) control Dlx expression in the telencephalon and diencephalon: URE2 and 112b in the Dlx1/Dlx2 bigene cluster, and I56i and I56ii in the Dlx5/Dlx6 bigene cluster. However, little is known so far with respect to the function of orthologous dlx genes and their regulatory elements during zebrafish GABAergic neuron development. To investigate whether similar dlx-mediated pathways exist in the early developing zebrafish forebrain, we generated independent lines of transgenic zebrafish carrying two distinct GFP reporter constructs driven by a beta-globin minimal promoter: one containing a similar to 1.4 kb dlx5a/dlx6a intergenic sequence (encompassing I56i and I56ii) and one with a similar to 1.1 kb fragment containing only the I56i CRE, respectively. The expression patterns of these two transgenes were compared with that obtained with another construct containing the similar to 1.4 kb dlx5a/dlx6a intergenic sequence and driven by a similar to 3.5 kb dlx6a 5'-flanking fragment. Our comparative analysis showed that GFP expression of the three transgene is largely overlapping throughout the ventral forebrain. Intriguingly, the dlx6a 5'-flanking fragment has a major impact on transgene expression in the mesencephalic tectum. Furthermore, comparison of transgene expression between the similar to 1.4 kb and similar to 1.1 kb intergenic fragments did not show any specific spatial expression conferred by I56ii. Almost all GFP-expressing cells in the transgenic zebrafish are GABA-positive and also express various GABAergic interneuron markers. Together, our data suggest that zebrafish dlx5a/dlx6a intergenic CREs may be involved in a conserved genetic pathway necessary for proper dlx expression during zebrafish GABAergic neuron development. (C) 2011 ISDN. Published by Elsevier Ltd. All rights reserved.Funding Information
- Canadian Institutes of Health Research (MOP14460)
This publication has 57 references indexed in Scilit:
- The relationship between dlx and gad1 expression indicates highly conserved genetic pathways in the zebrafish forebrainDevelopmental Dynamics, 2010
- Functional conservation of a forebrain enhancer from the elephant shark (Callorhinchus milii) in zebrafish and miceBMC Evolutionary Biology, 2010
- Role for TGF-β superfamily signaling in telencephalic GABAergic neuron developmentJournal of Neurodevelopmental Disorders, 2009
- Her6 regulates the neurogenetic gradient and neuronal identity in the thalamusProceedings of the National Academy of Sciences of the United States of America, 2009
- Dlx1&2 and Mash1 Transcription Factors Control MGE and CGE Patterning and Differentiation through Parallel and Overlapping PathwaysCerebral Cortex, 2009
- Conserved non-coding sequences and transcriptional regulationBrain Research Bulletin, 2008
- How Neuronal Migration Contributes to the Morphogenesis of the CNS: Insights from the ZebrafishDevelopmental Neuroscience, 2007
- Evaluating the biological relevance of putative enhancers using Tol2 transposon-mediated transgenesis in zebrafishNature Protocols, 2006
- Tangential Neuronal Migration Controls Axon Guidance: A Role for Neuregulin-1 in Thalamocortical Axon NavigationCell, 2006
- A phylotypic stage in vertebrate brain development: GABA cell patterns in zebrafish compared with mouseJournal of Comparative Neurology, 2005