Ernfors P, Van De Water T, Loring J, Jaenisch R
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142, USA.
Neuron. 1995 Jun;14(6):1153-64. doi: 10.1016/0896-6273(95)90263-5.
The physiological role of BDNF and NT-3 in the development of the vestibular and auditory systems was investigated in mice that carry a deleted BDNF and/or NT-3 gene. BDNF was the major survival factor for vestibular ganglion neurons, and NT-3, for spiral ganglion neurons. Lack of BDNF and NT-3 did not affect ingrowth of nerve fibers into the vestibular epithelium, but BDNF mutants failed to maintain afferent and efferent innervation. In the cochlea, BDNF mutants lost type 2 spiral neurons, causing an absence of outer hair cell innervation. NT-3 mutants showed a paucity of afferents and lost 87% of spiral neurons, presumably corresponding to type 1 neurons, which innervate inner hair cells. Double mutants had an additive loss, lacking all vestibular and spiral neurons. These results show that BDNF and NT-3 are crucial for inner ear development and, although largely coexpressed, have distinct and nonoverlapping roles in the vestibular and auditory systems.
在携带缺失BDNF和/或NT - 3基因的小鼠中,研究了BDNF和NT - 3在前庭和听觉系统发育中的生理作用。BDNF是前庭神经节神经元的主要存活因子,而NT - 3是螺旋神经节神经元的主要存活因子。缺乏BDNF和NT - 3并不影响神经纤维向内耳上皮的长入,但BDNF突变体无法维持传入和传出神经支配。在耳蜗中,BDNF突变体失去了2型螺旋神经元,导致外毛细胞神经支配缺失。NT - 3突变体显示传入神经稀少,失去了87%的螺旋神经元,推测这些神经元对应于支配内毛细胞的1型神经元。双突变体有累加性损失,缺乏所有前庭和螺旋神经元。这些结果表明,BDNF和NT - 3对内耳发育至关重要,尽管它们在很大程度上共同表达,但在前庭和听觉系统中具有不同且不重叠的作用。