Nothwang Hans Gerd, Ebbers Lena, Schlüter Tina, Willaredt Marc A
Neurogenetics group, Center of Excellence Hearing4All, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26111, Oldenburg, Germany,
Cell Tissue Res. 2015 Jul;361(1):33-48. doi: 10.1007/s00441-014-2110-7. Epub 2015 Jan 31.
A defining feature of the mammalian auditory system is the extensive processing of sound information in numerous ultrafast and temporally precise circuits in the hindbrain. By exploiting the experimental advantages of mouse genetics, recent years have witnessed an impressive advance in our understanding of developmental mechanisms involved in the formation and refinement of these circuits. Here, we will summarize the progress made in four major fields: the dissection of the rhombomeric origins of auditory hindbrain nuclei; the molecular repertoire involved in circuit formation such as Hox transcription factors and the Eph-ephrin signaling system; the timeline of functional circuit assembly; and the critical role of spontaneous activity for circuit refinement. In total, this information provides a solid framework for further exploration of the factors shaping auditory hindbrain circuits and their specializations. A comprehensive understanding of the developmental pathways and instructive factors will also offer important clues to the causes and consequences of hearing-loss related disorders, which represent the most common sensory impairment in humans.
哺乳动物听觉系统的一个显著特征是,在后脑众多超快速且时间精确的神经回路中对声音信息进行广泛处理。通过利用小鼠遗传学的实验优势,近年来我们对这些神经回路形成和完善过程中所涉及的发育机制的理解取得了令人瞩目的进展。在此,我们将总结在四个主要领域取得的进展:剖析听觉后脑核团的菱脑节起源;参与神经回路形成的分子组成,如Hox转录因子和Eph-ephrin信号系统;功能性神经回路组装的时间线;以及自发活动对神经回路完善所起的关键作用。总体而言,这些信息为进一步探索塑造听觉后脑神经回路及其特化的因素提供了坚实的框架。对发育途径和指导因素的全面理解也将为与听力损失相关疾病的病因和后果提供重要线索,这些疾病是人类最常见的感觉障碍。