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Math5-GFP转基因揭示的Math5和Math1的保守调控

Conserved regulation of Math5 and Math1 revealed by Math5-GFP transgenes.

作者信息

Hufnagel Robert B, Riesenberg Amy N, Saul Sara M, Brown Nadean L

机构信息

Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.

出版信息

Mol Cell Neurosci. 2007 Dec;36(4):435-48. doi: 10.1016/j.mcn.2007.08.006. Epub 2007 Aug 15.

Abstract

Retinal ganglion cell genesis requires the proneural bHLH transcription factor Math5 (Atoh7), but little is known about the regulatory elements that control its expression. Here, we investigate Math5 gene regulation using transgenic mice. These mice express GFP in the prenatal retina, live-labeling RGC axon migration and innervation of the brain. Unexpectedly, these Math5-GFP transgenes are also found in Math1 expression domains throughout the nervous system, intriguing since Math5 and Math1 normally exhibit nonoverlapping expression. Furthermore, Math5-GFP and Math1 are regulated similarly, by both Pax6 and Math1 itself, in the lower rhombic lip and dorsal spinal cord. We also show that Pax6 binds to particular Math5 and Math1 regulatory sequences in vitro. Together these data suggest that these atonal semi-orthologues may share conserved regulatory elements that are normally silent in the Math5 gene.

摘要

视网膜神经节细胞的生成需要神经前体bHLH转录因子Math5(Atoh7),但对于控制其表达的调控元件却知之甚少。在此,我们利用转基因小鼠研究Math5基因的调控。这些小鼠在产前视网膜中表达绿色荧光蛋白(GFP),对视网膜神经节细胞(RGC)轴突的迁移及向脑内的神经支配进行活体标记。出乎意料的是,这些Math5-GFP转基因在整个神经系统的Math1表达域中也有发现,这很有意思,因为Math5和Math1通常表现出不重叠的表达。此外,在菱唇下部和背侧脊髓中,Math5-GFP和Math1受Pax6和Math1自身的调控方式相似。我们还表明,Pax6在体外能与特定的Math5和Math1调控序列结合。这些数据共同表明,这些无调性半直系同源物可能共享保守的调控元件,而这些元件在Math5基因中通常是沉默的。

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