Analysis of transcriptional codes for zebrafish dopaminergic neurons reveals essential functions of Arx and Isl1 in prethalamic dopaminergic neuron development
Analysis of transcriptional codes for zebrafish dopaminergic neurons reveals essential functions of Arx and Isl1 in prethalamic dopaminergic neuron development
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DOI：
10.1016/j.ydbio.2012.06.010
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发表时间：
2012-09-01
影响因子：
2.7
通讯作者：
Driever, Wolfgang
中科院分区：
文献类型：
--
作者：
Filippi, Alida;Jainok, Chamaiphorn;Driever, Wolfgang
不同的多巴胺能神经元群在脑中的定义的解剖部位发育，以调节大量多样性的局部和远距离回路的功能。然而，从转录因子表达判断的分子身份尚未确定所有多巴胺能组。在这里，我们分析了区域表达的转录因子在斑马鱼幼虫的大脑，以确定共同表达与酪氨酸羟化酶标记多巴胺能神经元。我们定义的转录因子，清楚地确定每个多巴胺能组。这些数据证实了与哺乳动物系统定义的多巴胺能组的假定关系。我们专注于我们的功能分析前丘脑多巴胺能神经元，共表达的转录因子Arx和Isl1。基于吗啉的敲除揭示了Arx和Isl1都是丘脑前多巴胺能神经元发育所严格需要的，并且似乎是平行作用的。我们进一步表明，Arx有助于在丘脑前区的图案，而Isl1是所需的丘脑前多巴胺能神经元的分化。(c)2012 Elsevier Inc. All rights reserved.
Distinct groups of dopaminergic neurons develop at defined anatomical sites in the brain to modulate function of a large diversity of local and far-ranging circuits. However, the molecular identity as judged from transcription factor expression has not been determined for all dopaminergic groups. Here, we analyze regional expression of transcription factors in the larval zebrafish brain to determine co-expression with the Tyrosine hydroxylase marker in dopaminergic neurons. We define sets of transcription factors that clearly identify each dopaminergic group. These data confirm postulated relations to dopaminergic groups defined for mammalian systems. We focus our functional analysis on prethalamic dopaminergic neurons, which co-express the transcription factors Arx and Isl1. Morpholino-based knockdown reveals that both Arx and Isl1 are strictly required for prethalamic dopaminergic neuron development and appear to act in parallel. We further show that Arx contributes to patterning in the prethalamic region, while Isl1 is required for differentiation of prethalamic dopaminergic neurons. (c) 2012 Elsevier Inc. All rights reserved.