Regulation of cell fate and patterning in the developing mammalian cochlea.
Regulation of cell fate and patterning in the developing mammalian cochlea.
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DOI：
10.1097/moo.0b013e3283303347
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发表时间：
2009-10
影响因子：
1.6
通讯作者：
Puligilla C
中科院分区：
文献类型：
--
作者：
Kelley MW;Driver EC;Puligilla C
相当大比例的听力损失和耳聋是由Corti器官内细胞的结构或功能缺陷引起的。识别调控这一结构发育的分子因素，应该为了解内耳的形成和导致先天性听觉缺陷的信号通路提供有价值的见解。此外，对这些相同因素的靶向调节可以作为毛细胞再生的治疗方法。使用转基因和突变小鼠的实验结果，以及体外技术，已经确定了指定独特的听觉细胞类型(如毛细胞或支持细胞)或产生Corti器官特有的高度有序的细胞模式所需的基因和信号通路。特别是，刺猬和成纤维细胞生长因子信号通路调节祖细胞的形成，从而形成Corti器官。SOX2是一种转录因子，是形成耳蜗祖细胞群所必需的，矛盾的是，它也被证明是毛细胞发育的抑制因子。最后，运动蛋白肌球蛋白II调节Corti器官的伸展以及毛细胞和支持细胞的排列成有序的行。更好地了解指导耳蜗发育不同方面的信号通路，如特定的细胞命运或细胞模式，为确定可作为治疗干预目标的新途径或分子提供了可能性。
A significant proportion of hearing loss and deafness is caused by defects in the structure or function of cells within the organ of Corti. Identification of the molecular factors that regulate the development of this structure should provide valuable insights regarding inner ear formation and the signaling pathways that underlie congenital auditory deficits. In addition, targeted modulation of these same factors could be developed as therapies for hair cell regeneration. Results from experiments using transgenic and mutant mice, as well as in vitro techniques, have identified genes and signaling pathways that are required to either specify unique auditory cell types, such as hair cells or supporting cells, or to generate the highly ordered cellular pattern that is characteristic for the organ of Corti. In particular, the hedgehog and fibroblast growth factor signaling pathways modulate the formation of the progenitor cells that will give rise to the organ of Corti. Sox2, a transcription factor that is required for the formation of the cochlear progenitor cell population, has paradoxically been shown to also act as an inhibitor of hair cell development. Finally, the motor protein Myosin II regulates extension of the organ of Corti and the alignment of hair cells and supporting cells into ordered rows. A better understanding of the signaling pathways that direct different aspects of cochlear development, such as specific of cell fates or cellular patterning, offers the potential to identify new pathways or molecules that could be targeted for therapeutic interventions.