A novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusion

A novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusion
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斑马鱼腺体形成的新机制涉及肾上皮细胞转分化和活细胞挤出

DOI:
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发表时间:
2018
期刊:
bioRxiv
影响因子:
--
通讯作者:
A. Davidson
A. Davidson
中科院分区:
--
文献类型:
--
作者:
Richard W. Naylor;A. Davidson

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转分化是一种人们知之甚少的现象,即终末分化的细胞获得全新的身份。在这里,我们描述了斑马鱼自然发生的转分化的罕见例子,其中肾远端小管上皮细胞转化为称为斯坦尼乌斯小体(CS)的内分泌腺。我们发现这个过程需要Notch信号传导,并且与Hnf1b转录因子(肾小管命运的主调节因子)的细胞质隔离相关。 Irx3b 转录因子的缺陷导致远端小管细胞异位转分化为 CS 身份,但以 Notch 依赖性方式。使用活细胞成像,我们发现 CS 细胞集体经历顶端收缩,然后从肾小管中挤出形成一个独特的器官。该系统提供了一个有价值的新模型来理解转分化的分子和形态学基础,并将推动在治疗上利用这种罕见现象的努力。
Transdifferentiation is the poorly understood phenomenon whereby a terminally differentiated cell acquires a completely new identity. Here, we describe a rare example of a naturally occurring transdifferentiation in zebrafish in which kidney distal tubule epithelial cells are converted into an endocrine gland known as the Corpuscles of Stannius (CS). We find that this process requires Notch signalling and is associated with the cytoplasmic sequestration of the Hnf1b transcription factor, a master-regulator of renal tubule fate. A deficiency in the Irx3b transcription factor results in ectopic transdifferentiation of distal tubule cells to a CS identity but in a Notch-dependent fashion. Using live-cell imaging we show that CS cells undergo apical constriction en masse and are then extruded from the tubule to form a distinct organ. This system provides a valuable new model to understand the molecular and morphological basis of transdifferentiation and will advance efforts to exploit this rare phenomenon therapeutically.
DOI: 10.1681/asn.2012070756
发表时间: 2013-01-01
影响因子: 13.6
作者:
Naylor, Richard W.;Przepiorski, Aneta;Davidson, Alan J.
通讯作者: Davidson, Alan J.
DOI: --
发表时间: 2013-03
影响因子: 1.8
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发表时间: 1996-12
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