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 event in zebrafish in which kidney distal tubule epithelial cells are converted into an...

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Main Authors: Richard W Naylor, Hao-Han G Chang, Sarah Qubisi, Alan J Davidson
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-11-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/38911
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author Richard W Naylor
Hao-Han G Chang
Sarah Qubisi
Alan J Davidson
author_facet Richard W Naylor
Hao-Han G Chang
Sarah Qubisi
Alan J Davidson
author_sort Richard W Naylor
collection DOAJ
description 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.
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spelling doaj.art-65cd9f5935134c4dbfe22950007a3c782022-12-22T02:01:19ZengeLife Sciences Publications LtdeLife2050-084X2018-11-01710.7554/eLife.38911A novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusionRichard W Naylor0https://orcid.org/0000-0003-2901-7677Hao-Han G Chang1https://orcid.org/0000-0001-8023-6862Sarah Qubisi2Alan J Davidson3https://orcid.org/0000-0002-5732-1193Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New ZealandDepartment of Molecular Medicine and Pathology, University of Auckland, Auckland, New ZealandDepartment of Molecular Medicine and Pathology, University of Auckland, Auckland, New ZealandDepartment of Molecular Medicine and Pathology, University of Auckland, Auckland, New ZealandTransdifferentiation 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.https://elifesciences.org/articles/38911transdifferentiationkidneyendocrine glandHnf1bIrx3bNotch
spellingShingle Richard W Naylor
Hao-Han G Chang
Sarah Qubisi
Alan J Davidson
A novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusion
eLife
transdifferentiation
kidney
endocrine gland
Hnf1b
Irx3b
Notch
title A novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusion
title_full A novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusion
title_fullStr A novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusion
title_full_unstemmed A novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusion
title_short A novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusion
title_sort novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusion
topic transdifferentiation
kidney
endocrine gland
Hnf1b
Irx3b
Notch
url https://elifesciences.org/articles/38911
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