Riesenberg Amy N, Le Tien T, Willardsen Minde I, Blackburn David C, Vetter Monica L, Brown Nadean L
Division of Developmental Biology, Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio 45229, USA.
Genesis. 2009 Mar;47(3):175-87. doi: 10.1002/dvg.20479.
Activation of the bHLH factor Math5 (Atoh7) is an initiating event for mammalian retinal neurogenesis, as it is critically required for retinal ganglion cell formation. However, the cis-regulatory elements and trans-acting factors that control Math5 expression are largely unknown. Using a combination of transgenic mice and bioinformatics, we identified a phylogenetically conserved regulatory element that is required to activate Math5 transcription during early retinal neurogenesis. This element drives retinal expression in vivo, in a cross-species transgenic assay. Previously, Pax6 was shown to be necessary for the initiation of Math5 mRNA expression. We extend this finding by showing that the Math5 retinal enhancer also requires Pax6 for its activation, via Pax6 binding to a highly conserved binding site. In addition, our data reveal that other retinal factors are required for accurate regulation of Math5 by Pax6.
bHLH因子Math5（Atoh7）的激活是哺乳动物视网膜神经发生的起始事件，因为它是视网膜神经节细胞形成所必需的。然而，控制Math5表达的顺式调控元件和反式作用因子在很大程度上尚不清楚。通过结合转基因小鼠和生物信息学方法，我们鉴定出一个在系统发育上保守的调控元件，它是早期视网膜神经发生过程中激活Math5转录所必需的。在跨物种转基因实验中，该元件可驱动体内视网膜表达。此前研究表明，Pax6是Math5 mRNA表达起始所必需的。我们进一步发现，Math5视网膜增强子的激活也需要Pax6，Pax6通过结合一个高度保守的结合位点来实现这一作用。此外，我们的数据表明，其他视网膜因子对于Pax6精确调控Math5也是必需的。
