Balancing cell numbers during organogenesis: Six1a differentially affects neurons and sensory hair cells in the inner ear
Balancing cell numbers during organogenesis: Six1a differentially affects neurons and sensory hair cells in the inner ear
复制标题
DOI：
10.1016/j.ydbio.2011.06.035
复制
发表时间：
2011-09-01
影响因子：
2.7
通讯作者：
Collazo, Andres
中科院分区：
文献类型：
--
作者：
Bricaud, Olivier;Collazo, Andres
虽然参与机械感觉毛细胞和支配它们的神经元分化的基因已被识别，但参与平衡其相对数量的基因仍然未知。 Six1a 在这两个谱系中发挥双重作用，促进毛细胞命运，同时抑制神经元命运。与 Six1a 同源的基因可以充当转录激活子或阻遏子，具体取决于它们相互作用的伙伴。通过分析 Six1a 的假定蛋白质-蛋白质相互作用和 DNA 结合域中突变的体内和体外影响，我们发现，在发育中的斑马鱼内耳中，Six1a 通过充当转录激活子来促进毛细胞命运，并通过充当转录阻遏子来抑制神经元命运。我们还确定了 Six1a 的几个潜在合作伙伴，这些合作伙伴在这两个谱系之间有所不同。 Six1a 在耳囊发育中的双重作用提供了在内耳器官形成过程中平衡毛细胞和神经元相对数量的机制。 (C) 2011 Elsevier Inc. 保留所有权利。
While genes involved in the differentiation of the mechanosensory hair cells and the neurons innervating them have been identified, genes involved in balancing their relative numbers remain unknown. Six1a plays a dual role by promoting hair cell fate while inhibiting neuronal fate in these two lineages. Genes homologous to six1a act as either transcriptional activators or repressors, depending on the partners with which they interact. By assaying the in vivo and in vitro effects of mutations in presumptive protein-protein interacting and DNA-binding domains of Six1a, we show that, in the developing zebrafish inner ear, Six1a promotes hair cell fate by acting as a transcriptional activator and inhibits neuronal fate by acting as a transcriptional repressor. We also identify several potential partners for Six1a that differ between these two lineages. The dual role of Six1a in the developing otocyst provides a mechanism for balancing the relative number of hair cells and neurons during organogenesis of the inner ear. (C) 2011 Elsevier Inc. All rights reserved.