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

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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.

Data availability

The empirical counts for the experiments described in the manuscript are available as a spreadsheet on the Dryad database.

The following data sets were generated

1. Naylor RW
2. Davidson AJ
(2018) Data from: A novel mechanism of gland formation in zebrafish involving transdifferentiation of kidney cells and live cell extrusion
Dryad Digital Repository, doi:10.5061/dryad.3hp84t0.

http://dx.doi.org/10.5061/dryad.3hp84t0

Article and author information

Author details

Richard W Naylor

Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2901-7677
Hao-Han G Chang

Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand

Competing interests
The authors declare that no competing interests exist.
Sarah Qubisi

Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand

Competing interests
The authors declare that no competing interests exist.
Alan J Davidson

Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand

For correspondence
a.davidson@auckland.ac.nz

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5732-1193

Funding

Royal Society of New Zealand (RSNZ/JSP-UOA1401-JR)

Alan J Davidson

Health Research Council of New Zealand (HRC 15/057)

Alan J Davidson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study used zebrafish embryos, which were maintained and staged according to established protocols (Kimmel, Ballard, Kimmel, Ullmann, & Schilling, 1995) and in accordance with the University of Auckland's Animal Ethics Committee (protocol 001343).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.