University of Missouri Kansas City, School of Science and Engineering, Division of Biological and Biomedical Systems, Kansas City, MO 64110, USA.
Research Organisms, Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Biol Open. 2024 Sep 15;13(9). doi: 10.1242/bio.060580. Epub 2024 Sep 20.
Mechanosensory hair cells located in the inner ear mediate the sensations of hearing and balance. If damaged, mammalian inner ear hair cells are unable to regenerate, resulting in permanent sensory deficits. Aquatic vertebrates like zebrafish (Danio rerio) have a specialized class of mechanosensory hair cells found in the lateral line system, allowing them to sense changes in water current. Unlike mammalian inner ear hair cells, lateral line hair cells can robustly regenerate following damage. In mammals, the transcription factor Foxg1 functions to promote normal development of the inner ear. Foxg1a is expressed in lateral line sensory organs in zebrafish larvae, but its function during lateral line development and regeneration has not been investigated. Our study demonstrates that mutation of foxg1a results in slower posterior lateral line primordium migration and delayed neuromast formation. In developing and regenerating neuromasts, we find that loss of Foxg1a function results in reduced hair cell numbers, as well as decreased proliferation of neuromast cells. Foxg1a specifically regulates the development and regeneration of Islet1-labeled hair cells. These data suggest that Foxg1 may be a valuable target for investigation of clinical hair cell regeneration.
位于内耳的机械感觉毛细胞介导听觉和平衡感。如果受损,哺乳动物内耳毛细胞无法再生,导致永久性感觉缺陷。像斑马鱼(Danio rerio)这样的水生脊椎动物在侧线系统中有一种特殊的机械感觉毛细胞,使它们能够感知水流的变化。与哺乳动物内耳毛细胞不同,侧线毛细胞在受损后可以强烈再生。在哺乳动物中,转录因子 Foxg1 有助于促进内耳的正常发育。Foxg1a 在斑马鱼幼虫的侧线感觉器官中表达,但它在侧线发育和再生过程中的功能尚未被研究。我们的研究表明,foxg1a 的突变导致后部侧线原基迁移速度减慢和神经丘形成延迟。在发育和再生的神经丘中,我们发现 Foxg1a 功能的丧失导致毛细胞数量减少,以及神经丘细胞增殖减少。Foxg1a 特异性调节 Islet1 标记的毛细胞的发育和再生。这些数据表明,Foxg1 可能是研究临床毛细胞再生的有价值的靶点。