The ascl1a and dlx genes have a regulatory role in the development of GABAergic interneurons in the zebrafish diencephalon.

The ascl1a and dlx genes have a regulatory role in the development of GABAergic interneurons in the zebrafish diencephalon.
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DOI:
10.1016/j.ydbio.2013.05.025
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发表时间:
2013-09-01
影响因子:
2.7
通讯作者:
Ekker, Marc
Ekker, Marc
中科院分区:
生物学3区
文献类型:
--
作者:
MacDonald, Ryan B.;Pollack, Jacob N.;Debiais-Thibaud, Melanie;Heude, Eglantine;Talbot, Jared Coffin;Ekker, Marc

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在小鼠前脑中间神经元的发育过程中,Dlx基因在导致GABA能表型的基因调控网络(GRN)中起关键作用。在这里,我们研究了斑马鱼前脑中ascl 1a,dlx和gad 1b基因之间的调控关系。在前脑发育早期端脑和间脑中ascl 1a和dlx 1a的表达重叠。Ascl 1a功能的丧失导致dlx表达的丧失,以及随后在间脑前丘脑和下丘脑中dlx 5a和gad 1b表达的丧失。Dlx 1a和Dlx 2a功能的丧失,以及Dlx 5a和Dlx 6a在较小程度上的丧失,会损害前丘脑和下丘脑中gad 1b的表达。我们认为dlx 1a/2a作用于ascl 1a的下游,dlx 5a/dlx 6a和gad 1b的上游,激活GABA能特化。这条通路在间脑中是保守的,但在哺乳动物和端脑中的硬骨鱼之间有分歧。
During development of the mouse forebrain interneurons, the Dlx genes play a key role in a gene regulatory network (GRN) that leads to the GABAergic phenotype. Here, we have examined the regulatory relationships between the ascl1a, dlx, and gad1b genes in the zebrafish forebrain. Expression of ascl1a overlaps with dlx1a in the telencephalon and diencephalon during early forebrain development. The loss of Ascl1a function results in a loss of dlx expression, and subsequent losses of dlx5a and gad1b expression in the diencephalic prethalamus and hypothalamus. Loss of Dlx1a and Dlx2a function, and, to a lesser extent, of Dlx5a and Dlx6a, impairs gad1b expression in the prethalamus and hypothalamus. We conclude that dlx1a/2a act downstream of ascl1a but upstream of dlx5a/dlx6a and gad1b to activate GABAergic specification. This pathway is conserved in the diencephalon, but has diverged between mammals and teleosts in the telencephalon.
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