Karis A, Pata I, van Doorninck J H, Grosveld F, de Zeeuw C I, de Caprona D, Fritzsch B
Department of Animal Development and Systematics, University of Tartu, 51014 Tartu, Estonia.
J Comp Neurol. 2001 Jan 22;429(4):615-30. doi: 10.1002/1096-9861(20010122)429:4<615::aid-cne8>3.0.co;2-f.
Patterning the vertebrate ear requires the coordinated expression of genes that are involved in morphogenesis, neurogenesis, and hair cell formation. The zinc finger gene GATA-3 is expressed both in the inner ear and in afferent and efferent auditory neurons. Specifically, GATA-3 is expressed in a population of neurons in rhombomere 4 that extend their axons across the floor plate of rhombomere 4 (r4) at embryonic day 10 (E10) and reach the sensory epithelia of the ear by E13.5. The distribution of their cell bodies corresponds to that of the cell bodies of the cochlear and vestibular efferent neurons as revealed by labeling with tracers. Both GATA-3 heterozygous and GATA-3 null mutant mice show unusual axonal projections, such as misrouted crossing fibers and fibers in the facial nerve, that are absent in wild-type littermates. This suggests that GATA-3 is involved in the pathfinding of efferent neuron axons that navigate to the ear. In the ear, GATA-3 is expressed inside the otocyst and the surrounding periotic mesenchyme. The latter expression is in areas of branching of the developing ear leading to the formation of semicircular canals. Ears of GATA-3 null mutants remain cystic, with a single extension of the endolymphatic duct and no formation of semicircular canals or saccular and utricular recesses. Thus, both the distribution of GATA-3 and the effects of null mutations on the ear suggest involvement of GATA-3 in morphogenesis of the ear. This study shows for the first time that a zinc finger factor is involved in axonal navigation of the inner ear efferent neurons and, simultaneously, in the morphogenesis of the inner ear.
脊椎动物耳朵的模式形成需要参与形态发生、神经发生和毛细胞形成的基因的协调表达。锌指基因GATA-3在内耳以及传入和传出听觉神经元中均有表达。具体而言，GATA-3在菱脑节4的一群神经元中表达，这些神经元在胚胎第10天（E10）时将轴突延伸穿过菱脑节4（r4）的底板，并在E13.5时到达耳朵的感觉上皮。用示踪剂标记显示，它们的细胞体分布与耳蜗和前庭传出神经元的细胞体分布相对应。GATA-3杂合子和GATA-3基因敲除突变小鼠均显示出异常的轴突投射，如交叉纤维路线错误和面部神经中的纤维，而野生型同窝小鼠中则不存在这些情况。这表明GATA-3参与了导航至耳朵的传出神经元轴突的寻路过程。在耳朵中，GATA-3在耳囊中以及周围的耳周间充质中表达。后者的表达位于发育中耳朵的分支区域，这些区域会导致半规管的形成。GATA-3基因敲除突变小鼠的耳朵仍然呈囊状，内淋巴管只有单一延伸，没有形成半规管或球囊和椭圆囊隐窝。因此，GATA-3的分布以及基因敲除突变对耳朵的影响均表明GATA-3参与了耳朵的形态发生。这项研究首次表明，一种锌指因子参与了内耳传出神经元的轴突导航，同时也参与了内耳的形态发生。
