Ectopic Noggin blocks sensory and nonsensory organ morphogenesis in the chicken inner ear
Ectopic Noggin blocks sensory and nonsensory organ morphogenesis in the chicken inner ear
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DOI：
10.1006/dbio.1999.9457
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发表时间：
1999-12-01
影响因子：
2.7
通讯作者：
Wu, DK
中科院分区：
文献类型：
--
作者：
Chang, WS;Nunes, FD;Wu, DK
骨形态发生蛋白4（Bmp 4）在鸡内耳发育的多个阶段表达。在耳囊阶段，Bmp 4在每个假定的感觉器官中表达，以及在注定形成半规管的耳囊区域周围的间充质细胞中表达。在内耳的大体解剖结构形成之后，Bmp 4表达持续存在于一些感觉器官和半规管的限制域中。为了解决该基因在内耳发育中的作用，我们通过将其拮抗剂之一Noggin递送到卵内发育的内耳来阻断BMP 4功能。通过使用编码Noggin cDNA的复制型禽逆转录病毒（RCAS-N）或植入Noggin蛋白包被的珠子，将外源性Noggin递送到发育中的耳囊。头蛋白治疗导致各种表型，包括内耳的感觉和非感觉成分。在非感觉结构中，半规管对外源性Noggin最敏感，内淋巴管和内淋巴囊对外源性Noggin最不敏感。Noggin影响原始管外囊的增殖，以及管形成后的持续生长。此外，Noggin可能通过降低Msx 1和p75 NGFR表达影响嵴的结构模式。这些结果表明，BMP 4和可能的其他BMP是内耳发育的多个阶段所需的，（C）1999学术出版社。
Bone morphogenetic protein 4 (Bmp4) is expressed during multiple stages of development of the chicken inner ear. At the otocyst stage, Bmp4 is expressed in each presumptive sensory organ, as well as in the mesenchymal cells surrounding the region of the otocyst that is destined to form the semicircular canals. After the formation of the gross anatomy of the inner ear, Bmp4 expression persists in some sensory organs and restricted domains of the semicircular canals. To address the role of this gene in inner ear development, we blocked BMP4 function(s) by delivering one of its antagonists, Noggin, to the developing inner ear in ovo. Exogenous Noggin was delivered to the developing otocyst by using a replication-competent avian retrovirus encoding the Noggin cDNA (RCAS-N) or implanting beads coated with Noggin protein. Noggin treatment resulted in a variety of phenotypes involving both sensory and nonsensory components of the inner ear. Among the nonsensory structures, the semicircular canals were the most sensitive and the endolymphatic duct and sac most resistant to exogenous Noggin. Noggin affected the proliferation of the primordial canal outpouch, as well as the continual outgrowth of the canal after its formation. In addition, Noggin affected the structural patterning of the cristae, possibly via a decrease of Msx1 and p75NGFR expression. These results suggest that BMP4 and possibly other BMPs are required for multiple phases of inner ear development, (C) 1999 Academic Press.