Conserved and acquired features of neurogenin1 regulation
Conserved and acquired features of neurogenin1 regulation
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DOI：
10.1242/dev.01455
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发表时间：
2004-11-01
期刊：
影响因子：
4.6
通讯作者：
Str채hle, U
中科院分区：
文献类型：
--
作者：
Blader, P;Lam, CS;Str채hle, U
端脑在不同的脊椎动物群体中表现出巨大的形态差异。转录因子神经生成素1（ngn 1）控制着小鼠腭部的神经发生，也在进化上遥远的斑马鱼的端脑背侧表达。斑马鱼和哺乳动物ngn1基因座的上游区域含有几段保守序列。在这里，我们表明，斑马鱼ngn 1的上游区域能够忠实地重演内源性表达在斑马鱼和小鼠端脑。一个单一的保守的调控区是必不可少的背端脑表达的斑马鱼，并在背腭的小鼠的表达。然而，第二个保守的区域，这是在鱼端脑无活性是必要的表达在小鼠胚胎的侧腭。这个调控区，驱动表达在斑马鱼间脑和后脑，是依赖于Pax6的活性，并结合重组Pax6在体外。因此，ngn 1的调控元件似乎在脊椎动物中是保守的，在这些增强子的利用中存在一定的差异，用于在脊椎动物中获得更高级的功能。我们的数据提供了证据的共同选择的监管区域作为一种机制的进化多样化的表达模式，并建议在Pax6表达的改变是至关重要的新皮层的进化。
The telencephalon shows vast morphological variations among different vertebrate groups. The transcription factor neurogenin1 (ngn1) controls neurogenesis in the mouse pallium and is also expressed in the dorsal telencephalon of the evolutionary distant zebrafish. The upstream regions of the zebrafish and mammalian ngn1 loci harbour several stretches of conserved sequences. Here, we show that the upstream region of zebrafish ngn1 is capable of faithfully recapitulating endogenous expression in the zebrafish and mouse telencephalon. A single conserved regulatory region is essential for dorsal telencephalic expression in the zebrafish, and for expression in the dorsal pallium of the mouse. However, a second conserved region that is inactive in the fish telencephalon is necessary for expression in the lateral pallium of mouse embryos. This regulatory region, which drives expression in the zebrafish diencephalon and hindbrain, is dependent on Pax6 activity and binds recombinant Pax6 in vitro. Thus, the regulatory elements of ngn1 appear to be conserved among vertebrates, with certain differences being incorporated in the utilisation of these enhancers, for the acquisition of more advanced features in amniotes. Our data provide evidence for the co-option of regulatory regions as a mechanism of evolutionary diversification of expression patterns, and suggest that an alteration in Pax6 expression was crucial in neocortex evolution.