Abstract
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 event 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.
Highlights
Transdifferentiation is the poorly understood process by which a mature cell is converted to a completely different cell type (Tosh and Slack, 2002)
We have discovered a rare example of naturally occurring transdifferentiation that arises in the zebrafish embryonic kidney and results in the formation of endocrine cells from a differentiated renal tubular epithelium
By live-cell imaging, we show that the Corpuscles of Stannius (CS) cells are extruded from the tubule via apical constriction and mass cell extrusion
Summary
Transdifferentiation is the poorly understood process by which a mature cell is converted to a completely different cell type (Tosh and Slack, 2002). The process of transdifferentiation can be either direct, whereby a mature cell converts seamlessly into another mature cell type, or indirect, whereby there is a requirement for dedifferentiation to a more immature intermediary cell type, followed by differentiation into the new fate (Thowfeequ et al, 2007; Merrell and Stanger, 2016). Cases of indirect transdifferentiation in vertebrates include the well-known example of lens regeneration in amphibians following lentectomy (Stone, 1967), in which retinal pigmented epithelial cells initiate expression of pluripotency genes (Maki et al, 2009), dedifferentiate and mature into lens cells (Sanchez Alvarado and Tsonis, 2006). Indirect transdifferentiation is considered to occur in some cancers, via the epithelial-to-mesenchymal transition and dedifferentiation that often
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