Choo D, Sanne J L, Wu D K
Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland, 20850, USA.
Dev Biol. 1998 Dec 1;204(1):136-50. doi: 10.1006/dbio.1998.9095.
In order to examine the mechanisms that underlie development of the inner ear, the normal processes were perturbed using all-trans-retinoic acid (RA). By implanting a resin exchange bead saturated with RA into stage 16 (Hamburger and Hamilton, 1951, J. Morphol. 88, 49-92) embryonic day 2.5 chick ears, it was possible to analyze its in vivo effects on inner ear development. There is a temporal window during which the developing chick inner ear is particularly susceptible to the effects of RA (stages 16-19). This RA period of sensitivity precedes evidence of gross morphologic or histologic differentiation by at least 24 h, suggesting that mechanisms controlling formation of key inner ear structures are already in progress. There is a dose dependence on RA, with increasing doses of RA generating increasingly severe phenotypic abnormalities. Data indicate that these effects are due to differential sensitivities of the various inner ear structures to RA during their formation. In general, the vestibular structures were more susceptible to RA effects than the cochlear duct. Furthermore, nonsensory structures such as semicircular canals seemed to display a greater susceptibility to RA than their associated sensory structures (i.e., cristae). Among the three semicircular canals, the superior canal was the most susceptible to RA treatment, whereas the common crus was particularly resistant, suggesting that the molecular mechanisms for each structure's formation are different. The defect in semicircular canal formation is due to problems in the initial outgrowth of the canal plate which in turn is related to a down-regulation of early otocyst cell proliferation. This perturbation model provides valuable insight into the processes involved in producing the intricate patterning of the inner ear.
为了研究内耳发育的潜在机制，利用全反式视黄酸（RA）干扰正常发育过程。通过将浸有RA的树脂交换珠植入第16期（Hamburger和Hamilton，1951年，《形态学杂志》88卷，49 - 92页）鸡胚第2.5天的内耳中，就有可能分析其对体内内耳发育的影响。在鸡内耳发育过程中存在一个特定的时间窗，在此期间内耳对RA的影响特别敏感（第16 - 19期）。这个RA敏感时期至少比明显的形态学或组织学分化迹象提前24小时，这表明控制内耳关键结构形成的机制已经在进行中。RA存在剂量依赖性，随着RA剂量增加，产生的表型异常越来越严重。数据表明，这些影响是由于内耳各结构在形成过程中对RA的敏感性不同所致。一般来说，前庭结构比耳蜗管对RA的影响更敏感。此外，诸如半规管等非感觉结构似乎比其相关的感觉结构（即嵴）对RA更敏感。在三个半规管中，上半规管对RA处理最为敏感，而总脚则特别耐受，这表明每个结构形成的分子机制不同。半规管形成缺陷是由于管板最初生长出现问题，而这又与早期耳囊细胞增殖下调有关。这个干扰模型为内耳复杂模式形成过程提供了有价值的见解。
