Role of pitx genes in embryonic pattern formation

我们一直在研究一种调节基因Pitx3，它与人类的眼睛畸形和白内障有关。据推测，Pitx3通常会协调晶状体和视网膜形成所必需的其他基因的活动。当突变时，该基因在小鼠中具有类似的作用，然而迄今为止所有突变小鼠和人类患者都可能保留部分基因功能。Pitx3在青蛙中扮演着类似的角色，青蛙是一种经常被用来研究眼睛发育和遗传的生物。然而，我们注意到突变青蛙的其他异常，表明Pitx3在建立胚胎的身体计划中起着额外的作用：Pitx3在正确定位不对称的器官，如胃、肠、心脏、胆囊等方面起作用。此外，该基因似乎在调节椎骨前体的分割中起作用。我们采用了一种称为微阵列分析的技术来鉴定Pitx3活性的可能下游靶标（其他基因）。我们已经分离出了其中的一些基因，我们目前正试图了解Pitx3如何协调它们在构建眼睛、椎骨和不对称内脏器官的调节网络中的参与。描述与分割和左右不对称有关的基因网络对于帮助我们理解人类的脊柱、心脏和眼睛缺陷是如何产生的非常重要。

We have been studying a regulatory gene, Pitx3, that has been linked to eye malformations and cataracts in humans. Pitx3 presumably normally acts to coordinate the activities of other genes necessary to the formation of a lens and retina. When mutated, the gene has similar effects in mice, however all of the mutant mice and human patients characterized to date likely retain partial gene function. Pitx3 plays a similar role in frogs, an organism that is routinely employed to study eye development and genetics. However we have noticed other anomalies in mutant frogs that suggest additional roles for Pitx3 in establishing a body plan for embryos: Pitx3 plays a role in correctly orienting asymmetrical organs such as stomach, intestine, heart, gall bladder etc. In addition, the gene appears to play a role in regulating the segmentation of precursors to the vertebrae. We have employed a technique called microarray analysis to identify likely downstream targets (other genes) of Pitx3 activity. We have isolated some of these genes, and we are currently trying to understand how Pitx3 coordinates their participation in the regulatory networks that construct eye, vertebrae, and asymmetrical visceral organs. Characterizing the gene networks involved in segmentation and left/right asymmetry is important for helping us to understand how spinal, heart, and eye defects arise in humans.