Conditional deletion of N-Myc disrupts neurosensory and non-sensory development of the ear.

Conditional deletion of N-Myc disrupts neurosensory and non-sensory development of the ear.
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DOI:
10.1002/dvdy.22620
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发表时间:
2011-06
影响因子:
2.5
通讯作者:
Fritzsch, Bernd
Fritzsch, Bernd
中科院分区:
生物学3区
文献类型:
--
作者:
Kopecky, Benjamin;Santi, Peter;Johnson, Shane;Schmitz, Heather;Fritzsch, Bernd

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耳朵发育需要转录因子的相互作用以促进增殖和分化。原癌基因N-Myc是Myc家族中调控细胞增殖的成员。为了研究N-Myc的功能,我们用Tg(Pax2-Cre)和Foxg 1KiCre有条件地敲除了耳朵中的N-Myc。N-Myc CKO表现为耳生长减慢、感觉上皮融合、组织学紊乱、神经支配紊乱等异常形态。使用薄片激光成像显微镜(TSLIM),三维重建和量化显示耳蜗大小减少了50%以上。免疫组织化学和原位杂交显示妊娠器官-耳蜗器融合,顶端呈“环状”,内、外毛细胞不明显。此外,发育异常的耳蜗基底端附近的前庭神经节也有交叉神经支配。这些发现是在N-Myc与其他一些细胞增殖和命运决定基因在耳朵发育过程中可能的功能关系的背景下提出的。
Ear development requires interactions of transcription factors for proliferation and differentiation. The proto-oncogene N-Myc is a member of the Myc family that regulate proliferation. To investigate the function of N-Myc, we conditionally knocked out N-Myc in the ear using Tg(Pax2-Cre) and Foxg 1KiCre. N-Myc CKOs had reduced growth of the ear, abnormal morphology including fused sensory epithelia, disrupted histology, and disorganized neuronal innervation. Using Thin-Sheet Laser Imaging Microscopy (TSLIM), 3D reconstruction and quantification of the cochlea revealed a greater than fifty percent size reduction. Immunochemistry and in situ hybridization showed a gravistatic organ-cochlear fusion and a “circularized” apex with no clear inner and outer hair cells. Furthermore, the abnormally developed cochlea had cross innervation from the vestibular ganglion near the basal tip. These findings are put in the context of the possible functional relationship of N-Myc with a number of other cell proliferative and fate determining genes during ear development.
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