Downstream targets of GATA3 in the vestibular sensory organs of the inner ear.

Downstream targets of GATA3 in the vestibular sensory organs of the inner ear.
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GATA3的下游靶标在内耳的前庭感觉器官中。

DOI:
10.1002/dvdy.22149
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发表时间:
2009-12
影响因子:
2.5
通讯作者:
Lovett, Michael
Lovett, Michael
中科院分区:
生物学3区
文献类型:
--
作者:
Alvarado, David M.;Veile, Rose;Speck, Judith;Warchol, Mark;Lovett, Michael

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转录因子GATA3的单倍不足导致人类听力损失。它在整个听觉感觉上皮(SE)中表达。在前庭器官中,GATA 3仅限于椭圆囊的纹状体反转区。静纤毛方向在该区域发生180°的偏移,该区域包含形态上不同的I型毛细胞。条纹在所有的反纹动物中是保守的,其功能尚不清楚,GATA 3是唯一已知的反转区标记。为了鉴定可能指向纹状体功能的GATA 3的下游靶标,我们测量了纹状体和纹状体外SE之间的基因表达差异。将这些与GATA3 RNAi和GATA3过表达后的谱进行比较。我们鉴定了与GATA 3一致变化的四个基因(BMP 2、FKHL 18、LMO 4和MBNL 2)。其中两个(LMO4和MBNL2)被证明是GATA 3的直接靶标。我们的研究结果表明,GATA3影响WNT信号在这个区域的感觉黄斑。
Haploinsufficiency for the transcription factor GATA3 leads to hearing loss in humans. It is expressed throughout the auditory sensory epithelium (SE). In the vestibular organs, GATA3 is limited to the striola reversal zone of the utricle. Stereocilia orientation shifts 180° at this region which contains morphologically-distinct type I hair cells. The striola is conserved in all amniotes, its function is unknown and GATA3 is the only known marker of the reversal zone. To identify downstream targets of GATA3 that might point to striolar function we measured gene expression differences between striolar and extra-striolar SE. These were compared with profiles after GATA3 RNAi and GATA3 over-expression. We identified four genes (BMP2, FKHL18, LMO4 and MBNL2) that consistently varied with GATA3. Two of these (LMO4 and MBNL2) were shown to be direct targets of GATA3 by ChIP. Our results suggest that GATA3 impacts WNT signaling in this region of the sensory macula.
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