Abstract：
The process of valve formation is a complex process that involves intricate interplay between various pathways at precise times. Although we have not completely elucidated the molecular pathways that lead to normal valve formation, we have identified a few major players in this process. We are now able to implicate TGF-ß, BMP, and NOTCH as suspects in tricuspid atresia (TA), as well as their downstream targets: NKX2-5, TBX5, NFATC1, GATA4, and SOX9. We know that the TGF-ß and the BMP pathways converge on the SMAD4 molecule, and we believe that this molecule plays a very important role to tie both pathways to TA. Similarly, we look at the NOTCH pathway and identify the HEY2 as a potential link between this pathway and TA. Another transcription factor that has been implicated in TA is NFATC1. While several mouse models exist that include part of the TA abnormality as their phenotype, no true mouse model can be said to represent TA. Bridging this gap will surely shed light on this complex molecular pathway and allow for better understanding of the disease process.
摘要：
瓣膜形成的过程是复杂的过程,其涉及在精确时间的各种途径之间的复杂的相互作用。虽然我们还没有完全阐明导致正常瓣膜形成的分子途径，我们已经确定了这个过程中的几个主要参与者。我们现在能够暗示TGF-β，BMP,和NOTCH怀疑三尖瓣闭锁（TA），以及它们的下游目标：NKX2-5、TBX5、NFATC1、GATA4和SOX9。我们知道TGF-β和BMP途径在SMAD4分子上汇聚，我们认为这种分子在将两种途径与TA联系起来方面起着非常重要的作用。同样，我们研究了NOTCH途径,并将HEY2确定为该途径与TA之间的潜在联系.与TA有关的另一种转录因子是NFATC1。虽然存在几种小鼠模型，包括部分TA异常作为其表型，没有真正的小鼠模型可以说代表TA。弥合这一差距肯定会阐明这一复杂的分子途径，并有助于更好地了解疾病过程。
