Genetics and morphology of the middle ear ossicles in the developing mouse embryo

我对研究中耳听小骨是如何发育的很感兴趣。这些听小骨的缺陷，如融合，是相当常见的，并导致听力问题。这些缺陷可以通过使用CT（计算机断层扫描）扫描来观察，这可以评估患者是否适合进行矫正性耳部手术。中耳由三个小骨组成，它们形成连接鼓膜和内耳的链条。三个听小骨由关节连接，关节可能畸形或缺失，导致中耳融合和听力损失。在这些患者中，尚不清楚所观察到的缺陷是如何产生的。这是由于缺乏关于这些关节在正常发育过程中形成的信息。本研究试图通过研究中耳，首先在正常小鼠胚胎中，然后在突变小鼠胚胎中，来纠正我们知识中的这一缺陷。小鼠中耳的发育与人类相似，因此使用小鼠模型获得的信息与人类患者直接相关。我计划主要集中在前两个听小骨和关节区域，因为这是最常发生缺陷的区域。我们首先想知道：sum关节如何形成sum关节形成涉及哪些基因sum关节的位置如何决定sum三个听小骨中的每一个如何发展它们各自的特徴（即彼此之间的差异）在确定了中耳的这一区域通常是如何形成的之后，我们将利用这些信息来调查有中耳炎的病例。异常为此，我们将分析一个在TCOF1基因中有突变的小鼠胚胎。该基因缺陷的患者发展为Treacher柯林斯综合征（TCS），其与几乎100%的病例中的融合中耳和听力损失相关。这项工作应该给出一个清晰的图片，如何在TCS中看到中耳缺陷发生在胚胎学。最终，这些信息可以帮助TCS患者在讨论手术选择时做出更明智的决定。

I am interested in researching how the middle ear ossicles develop. Defects in these ossicles, such as fusion, are fairly common and lead to hearing problems. These defects can be seen by using CT (computed tomography) scans, which allow assessment of the patient s suitability for corrective ear surgery. The middle ear is composed of three ossicles that form a chain linking the ear drum with the inner ear. The three ossicles are connected by joints, which can be malformed or absent, resulting in fusion of the middle ear and hearing loss. In these patients it is unclear how the defects observed arose. This is due to a lack of information available with respect to formation of these joints during normal development.This research attempts to correct this deficit in our knowledge by investigating the middle ear, first in normal and then in mutant mouse embryos. Development of the mouse middle ear has been shown to be similar to that of humans and therefore information obtained from using mouse models can be directly related to human patients. I plan to concentrate mainly on the first two ossicles and joint region, as this is the region where defects most often occur. We would first like to know: sum How the joint forms sum What genes are involved in joint formation sum How is the position of the joint determined sum How do each of the three ossicles develop their individual specification (ie their difference from each other) during normal embryonic development.Having identifies how this region of the middle ear normally forms we will use this information to investigate cases where there is an abnormality. For this we will be analysing a mouse embryo that has a mutation in a gene called TCOF1. Patients with defects in this gene develop Treacher Collins syndrome (TCS) which is associated with a fused middle ear and hearing loss in almost 100% of cases. This work should give a clear picture of how the middle ear defects seen in TCS occur during embryology. Ultimately, such information may help patients with TCS by allowing for a more informed decision when the option for surgery is discussed.