The transcription factor six1 inhibits neuronal and promotes hair cell fate in the developing zebrafish (Danio rerio) inner ear
The transcription factor six1 inhibits neuronal and promotes hair cell fate in the developing zebrafish (Danio rerio) inner ear
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DOI：
10.1523/jneurosci.1025-06.2006
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发表时间：
2006-10-11
影响因子：
5.3
通讯作者：
Collazo, Andres
中科院分区：
文献类型：
--
作者：
Bricaud, Olivier;Collazo, Andres
导致机械感觉毛细胞和状态听神经节神经元从早期的耳上皮细胞分化的发育过程尚不清楚。可能的候选者包括Pax-Six-Eya-Dach(配对框-正弦Oculis同源框-眼睛缺失-腊肠)基因调控网络的成员。我们克隆了斑马鱼SIX1，并对其在内耳发育中的功能进行了研究。获得和丧失功能的实验表明，SIX1在毛细胞和神经细胞谱系中具有相反的作用。它促进毛细胞的命运，反过来，通过不同地影响这些谱系中的细胞增殖和细胞死亡，抑制神经元的命运。通过单独靶向具有atoh1a(无调性同源1a)基因敲除的毛细胞或具有Neurog1(神经原蛋白1)基因敲除的神经元，我们发现剩余的细胞群、神经元或毛细胞分别仍然受到SIX1功能的增强或丧失的影响。SIX1与Pax-Six-Eya-Dach调控网络的其他成员相互作用，特别是毛细胞中的Dacha和Dachb，但不是神经元谱系。与小鼠不同，SIX1似乎不依赖于EYA1，尽管它似乎对腹侧上皮中EYA1和pax2b的表达调节很重要。此外，SIX1的表达似乎受到pax2b和foxi1(叉头盒II)的调节，正如预期的那样，它是耳道胎盘的早期诱导者。我们的结果首次证明了Pax-Six-Eya-Dach调控网络成员在内耳发育中的双重作用。
The developmental processes leading to the differentiation of mechanosensory hair cells and statoacoustic ganglion neurons from the early otic epithelium remain unclear. Possible candidates include members of the Pax-Six-Eya-Dach (paired box-sine oculis homeobox-eyes absent-dachshund) gene regulatory network. We cloned zebrafish six1 and studied its function in inner ear development. Gain- and loss-of-function experiments show that six1 has opposing roles in hair cell and neuronal lineages. It promotes hair cell fate and, conversely, inhibits neuronal fate by differentially affecting cell proliferation and cell death in these lineages. By independently targeting hair cells with atoh1a ( atonal homolog 1a) knockdown or neurons with neurog1 ( neurogenin 1) knockdown, we showed that the remaining cell population, neurons or hair cells, respectively, is still affected by gain or loss of six1 function. six1 interacts with other members of the Pax-Six-Eya-Dach regulatory network, in particular dacha and dachb in the hair cell but not neuronal lineage. Unlike in mouse, six1 does not appear to be dependent on eya1, although it seems to be important for the regulation of eya1 and pax2b expression in the ventral otic epithelium. Furthermore, six1 expression appears to be regulated by pax2b and also by foxi1 (forkhead box II) as expected for an early inducer of the otic placode. Our results are the first to demonstrate a dual role for a member of the Pax-Six-Eya-Dach regulatory network in inner ear development.