Prevention of cleft palate: the critical role of p63 and IRF6 signalling

预防腭裂：p63 和 IRF6 信号传导的关键作用

• 批准号: G0901539/1
• 负责人: Michael Dixon
• 金额: $ 86.11万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0901539%2F1
• 关键词: Prevention; cleft; palate; critical; role

The palate (the roof of the mouth) develops from two distinct parts that fuse together during development of the baby. 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 corrected 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 aim of this project is to study the way in which two genes, designated p63 and IRF6, function together during development of the palate. So far, we have discovered that p63 switches on the function of IRF6 and that this, in turn, causes the levels of p63 to drop just before fusion of the two halves of the palate. In our initial studies, we will determine whether or not cleft palate results when p63 is maintained at an artificially high level in the palate of developing mice. Subsequently, we will obtain a more complete picture of the ways in which the palate develops by discovering the target genes controlled by p63 and IRF6. 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 may help us to provide improved genetic diagnosis and counselling to patients and their families who are affected by this distressing condition.

上颚（口腔的上颚）由两个不同的部分组成，在婴儿的发育过程中融合在一起。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有困难，可以通过长期手术、牙科治疗和语言治疗在一定程度上得到纠正；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。该项目的目的是研究p63和IRF6两个基因在上颚发育过程中的共同作用方式。到目前为止，我们已经发现p63开启了IRF6的功能，而这反过来又导致p63的水平在上颚的两半融合之前下降。在我们的初步研究中，我们将确定当p63在发育小鼠的上颚维持在人为的高水平时是否会导致腭裂。随后，我们将通过发现p63和IRF6控制的靶基因，对上颚发育的方式有更全面的了解。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，这些信息可以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遗传诊断和咨询。