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

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 ad
vance efforts to exploit thi...

转分化（Transdifferentiation）是一种尚未被充分阐明的生物学现象，指终末分化细胞获得全新细胞身份的过程。本研究报道了斑马鱼中一例罕见的自然转分化事件：肾脏远端小管上皮细胞可转化为一种名为斯坦尼修斯小体（Corpuscles of Stannius, CS）的内分泌腺体。

研究发现，该过程依赖Notch信号通路（Notch signalling），且伴随Hnf1b转录因子的细胞质滞留——该转录因子是肾小管细胞命运的主控调控因子。Irx3b转录因子的缺失会导致远端小管细胞异位转分化为斯坦尼修斯小体细胞，但这一过程仍以Notch信号通路依赖的方式进行。

借助活细胞成像（live-cell imaging）技术，我们证实斯坦尼修斯小体细胞会成群发生顶端收缩（apical constriction），随后从肾小管中脱离并最终形成独立的器官。

本研究体系为解析转分化的分子与形态学基础提供了极具价值的新型模型，将推动针对该过程的开发利用相关研究……