Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, Rockville, Maryland, USA.
Dev Dyn. 2010 Feb;239(2):505-13. doi: 10.1002/dvdy.22200.
The mammalian organ of Corti of the inner ear is a highly sophisticated sensory end organ responsible for detecting sound. Noggin is a secreted glycoprotein, which antagonizes bone morphogenetic proteins 2 and 4 (Bmp2 and Bmp4). The lack of this antagonist causes increased rows of inner and outer hair cells in the organ of Corti. In mice, Bmp2 is expressed transiently in nascent cochlear hair cells. To investigate whether Noggin normally modulates the levels of Bmp2 for hair cell formation, we deleted Bmp2 in the cochlear hair cells using two cre strains, Foxg1(cre/+) and Gfi1(cre/+). Bmp2 conditional knockout cochleae generated using these two cre strains show normal hair cells. Furthermore, Gfi1(cre/+);Bmp2(lox/-) mice are viable and have largely normal hearing. The combined results of Noggin and Bmp2 mutants suggest that Noggin is likely to regulate other Bmps in the cochlea such as Bmp4.
哺乳动物内耳的 Corti 器官是一种高度复杂的感觉末梢器官,负责检测声音。 Noggin 是一种分泌的糖蛋白,能拮抗骨形态发生蛋白 2 和 4(Bmp2 和 Bmp4)。缺乏这种拮抗剂会导致 Corti 器官中的内毛细胞和外毛细胞行数增加。在小鼠中,Bmp2 在内耳毛细胞中短暂表达。为了研究 Noggin 是否正常调节 Bmp2 水平以形成毛细胞,我们使用两种 cre 株系 Foxg1(cre/+)和 Gfi1(cre/+),在耳蜗毛细胞中删除了 Bmp2。使用这两种 cre 株系生成的 Bmp2 条件性敲除耳蜗显示出正常的毛细胞。此外,Gfi1(cre/+);Bmp2(lox/-)小鼠是存活的,并且听力基本正常。 Noggin 和 Bmp2 突变体的综合结果表明,Noggin 可能会调节耳蜗中的其他 Bmps,如 Bmp4。