Abstract
In order to generate a zebrafish model of β cell regeneration, we have expressed an Escherichia coli gene called nfsB in the β cells of embryonic zebrafish. This bacterial gene encodes a nitroreductase (NTR) enzyme, which can convert prodrugs such as metronidazole (Met) to cytotoxins. By fusing nfsB to mCherry, we can simultaneously render β cells susceptible to prodrug and visualize Met dependent cell ablation. We show that the neighboring α and δ cells are unaffected by prodrug treatment and that ablation is β cell specific. Following drug removal and 36 h of recovery, β cells regenerate. Using ptf1a morphants, it is clear that this β cell recovery occurs independently of the presence of the exocrine pancreas. Also, by using photoconvertible Kaede to cell lineage trace and BrdU incorporation to label proliferation, we investigate mechanisms for β regeneration. Therefore, we have developed a unique resource for the study of β cell regeneration in a living vertebrate organism, which will provide the opportunity to conduct large-scale screens for pharmacological and genetic modifiers of β cell regeneration.
Original language | English (US) |
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Pages (from-to) | 218-229 |
Number of pages | 12 |
Journal | Mechanisms of Development |
Volume | 124 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2007 |
Externally published | Yes |
Keywords
- Cell lineage tracing
- Diabetes
- Differentiation
- Disease model
- Prodrug
- Regeneration
ASJC Scopus subject areas
- Embryology
- Developmental Biology