Progenitor potential of nkx6.1-expressing cells throughout zebrafish life and during beta cell regeneration

BMC Biology
Aurélie P GhayeI Manfroid

Abstract

In contrast to mammals, the zebrafish has the remarkable capacity to regenerate its pancreatic beta cells very efficiently. Understanding the mechanisms of regeneration in the zebrafish and the differences with mammals will be fundamental to discovering molecules able to stimulate the regeneration process in mammals. To identify the pancreatic cells able to give rise to new beta cells in the zebrafish, we generated new transgenic lines allowing the tracing of multipotent pancreatic progenitors and endocrine precursors. Using novel bacterial artificial chromosome transgenic nkx6.1 and ascl1b reporter lines, we established that nkx6.1-positive cells give rise to all the pancreatic cell types and ascl1b-positive cells give rise to all the endocrine cell types in the zebrafish embryo. These two genes are initially co-expressed in the pancreatic primordium and their domains segregate, not as a result of mutual repression, but through the opposite effects of Notch signaling, maintaining nkx6.1 expression while repressing ascl1b in progenitors. In the adult zebrafish, nkx6.1 expression persists exclusively in the ductal tree at the tip of which its expression coincides with Notch active signaling in centroacinar/terminal end duct cell...Continue Reading

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Citations

Mar 11, 2016·Developmental Biology·Rebecca L BeerMeritxell Rovira
Apr 27, 2016·Scientific Reports·Surjya Narayan DashSanna Lehtonen
Nov 14, 2016·Molecular and Cellular Endocrinology·Solomon Afelik, Meritxell Rovira
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Mar 21, 2019·Animal Models and Experimental Medicine·Yu-Qiong ZhaoHua Chen
Aug 23, 2018·Development, Growth & Differentiation·Hiroki Matsuda
Oct 5, 2017·Nature Communications·Danhua ZhangP Duc Si Dong
Jan 16, 2021·Biomedicines·Laura MassozIsabelle Manfroid
Mar 12, 2021·Human Molecular Genetics·Hannah E EdelmanMichael J Parsons
Jun 9, 2021·Nature Communications·Christos KarampeliasOlov Andersson
Jul 3, 2020·Cell Regeneration·Bingyuan YangWenbiao Chen

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Methods Mentioned

BETA
transgenic
RNA-seq
fluorescence-activated cell sorting
PCR
in vitro transcription
genotyping
FACS
Illumina sequencing
chip

Software Mentioned

Ensembl
Photoshop
Tophat
Imaris
R package EBSeq
ZiFiT

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