Role of Bone Morphogenetic Protein Genes in Patterning the Developing Inner Ear

脊椎动物的内耳是一个复杂的迷宫，由充满液体的管道、囊和导管包裹在骨骼中。这些器官含有感觉毛细胞和支持细胞，帮助平衡和运动控制，有些部分专门用于听力，如在哺乳动物的耳蜗里。这种复杂的三维结构是在胚胎发育过程中产生的，它来自头部一侧的一块增厚的扁平斑块，称为胎座。目前还不清楚是什么基因参与了这些从最初简单的皮肤斑块中产生的、经过精心设计的管子和袋子的发育程序。初步结果表明，两种蛋白质之间存在重要的相互作用，一种被称为‘骨形态发生蛋白#4’(BMP4)，另一种被称为‘noggin’，它可能作为一对拮抗的图案化调节器。该项目利用解剖学、遗传学和分子生物学以及新的显微外科技术，将含有蛋白质表达细胞的微小珠子直接植入发育中的耳朵。结果将阐明特定蛋白质的遗传表达如何塑造复杂感官的形态。这项工作将对神经科学的几个领域产生影响，该项目还将为学生提供多学科培训。

The inner ear of vertebrates is a complex labyrinth of fluid-filled canals, pouches and ducts encased in bone. These organs contain sensory hair cells and supporting cells, and aid in balance and movement control, with some parts specialized for hearing, as in the cochlea of mammals. This complex three-dimensional structure arises during embryonic development from a thickened flat patch called a placode on the side of the head. It is unclear what genes are involved in the developmental program for these precisely 'engineered' tubes and pouches from this originally simple patch of skin. Preliminary results suggest that there are important interactions between two proteins, one called 'bone-morphogenetic protein #4' (BMP4) and the other called 'noggin' that may act as an antagonistic pair of regulators for patterning. This project utilizes anatomical, genetic and molecular biology along with novel microsurgical techniques to implant tiny beads containing the protein-expressing cells directly in the developing ear. Results will clarify how genetic expression of particular proteins can shape the morphology of a complex sensory organ. This work will have an impact in several areas of neuroscience, and the project also will provide multidisciplinary training for students.