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

上颚（口腔的顶部）是由胚胎发育过程中融合在一起的两个部分发育而来的。目前，我们还不完全了解是什么控制了这些事件，但我们知道，常见的和令人痛苦的出生缺陷腭裂的结果时，融合的两个半腭未能发生。腭裂患者在进食和说话方面存在困难，通过长期手术、牙科治疗和语言治疗，这些问题可以得到一定程度的改善。因此，我们有必要了解基因在正常发育过程中如何协同工作，以及这些基因在腭裂中如何受到影响。Sonic Hedgehog蛋白是确保腭裂正常发育的关键分子。然而，只有一小部分响应Sonic Hedgehog的蛋白质被鉴定出来。最近，已经开发出的方法将使我们能够识别由Sonic Hedgehog控制的完整蛋白质组。我们将使用这些技术来剖析Sonic Hedgehog信号在确保腭部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，我们将在小鼠中进行这些实验，其中腭的发育与人类完全相同。在短期内，这项研究将帮助我们了解腭部正常发育的基础过程，以及这些过程在腭裂中是如何被破坏的。从长远来看，这些信息将有助于我们为受这种令人痛苦的疾病影响的患者及其家人提供更好的诊断、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.