Dissecting the role of sonic hedgehog signalling during development of the secondary palate: a systems-level approach

上颚（上颚）由胚胎发育时融合在一起的两半发育而成。目前，我们还不完全了解是什么控制了这些事件，但我们确实知道，当两半腭裂未能发生融合时，就会出现常见而令人痛苦的先天缺陷腭裂。腭裂患者在进食和说话方面存在困难，可以通过长期手术、牙科治疗和语言治疗在一定程度上改善；因此，我们有必要了解基因在正常发育过程中是如何协同工作的，以及这些基因在腭裂中是如何受到影响的。Sonic Hedgehog蛋白是确保上颚正常发育的关键分子；然而，只有一小部分蛋白质对Sonic Hedgehog有反应。最近，已经开发出的方法将使我们能够识别由Sonic Hedgehog控制的整套蛋白质。我们将使用这些技术来解剖Sonic Hedgehog信号在确保腭裂正确发育从而防止腭裂中的作用。为了确保这项研究在道德上完成，我们将在老鼠身上进行这些实验，在老鼠身上，上颚的发育方式与人类完全相同。在短期内，这项研究将帮助我们了解腭正常发育的过程，以及这些过程在腭裂中是如何被破坏的。从长远来看，这些信息将帮助我们为受这种痛苦状况影响的患者及其家属提供更好的诊断、遗传咨询和治疗。

The palate (the roof of the mouth) develops from two halves that fuse together during embryonic development. Currently, we do not completely understand what controls these events, but we do know that the common and distressing birth defect cleft palate results when fusion of the two halves of the palate fails to occur. Patients with cleft palate experience difficulties with eating and speaking, which can be improved to some degree by long-term surgery, dental treatment, and speech therapy; it is therefore essential that we have more information on how genes work together during normal development and how these are affected in cleft palate.The Sonic Hedgehog protein is a key molecule in ensuring that the palate develops normally; however, only a small fraction of proteins acting in response to Sonic Hedgehog has been identified. Recently, methods have been developed that will allow us to identify the complete set of proteins controlled by Sonic Hedgehog. We will use these techniques to dissect the role of Sonic Hedgehog signalling in ensuring that the palate develops correctly thereby preventing cleft palate. To ensure that this research is completed ethically, we will perform these experiments in mice, in which the palate develops in exactly the same way as in humans. In the short-term, this research will help us to understand the processes that underlie normal development of the palate and how these are disrupted in cleft palate. In the longer term, this information will help us to provide improved diagnosis, genetic counselling and treatment to patients and their families who are affected by this distressing condition.