PUBLICATION

Disruption of the pancreatic vasculature in zebrafish affects islet architecture and function

Authors
Mullapudi, S.T., Boezio, G.L.M., Rossi, A., Marass, M., Matsuoka, R.L., Matsuda, H., Helker, C.S.M., Yang, Y.H.C., Stainier, D.Y.R.
ID
ZDB-PUB-191011-21
Date
2019
Source
Development (Cambridge, England)   146(21): (Journal)
Registered Authors
Helker, Christian, Matsuda, Hiroki, Matsuoka, Ryota, Stainier, Didier
Keywords
Beta cells, Pancreas, VEGF, Vasculature, Zebrafish
MeSH Terms
  • Transgenes
  • Islets of Langerhans/cytology*
  • Green Fluorescent Proteins/metabolism
  • Mutation
  • Zebrafish
  • Vascular Endothelial Growth Factor A/metabolism
  • Blood Glucose/analysis
  • Ligands
  • Gene Expression Regulation, Developmental
  • Zebrafish Proteins/metabolism
  • Glucose Tolerance Test
  • Microscopy, Fluorescence
  • Vascular Endothelial Growth Factor Receptor-1/metabolism
  • Animals
  • Pancreas/blood supply*
  • Pancreas/embryology
  • Glucose/metabolism
(all 17)
PubMed
31597659 Full text @ Development
Abstract
A dense local vascular network is crucial for pancreatic endocrine cells to sense metabolites and secrete hormones, and understanding the interactions between the vasculature and the islets may allow for therapeutic modulation in disease conditions. Using live imaging in two models of vascular disruption in zebrafish, we identified two distinct roles for the pancreatic vasculature. At larval stages, expression of a dominant negative version of Vegfaa (dnVegfaa) in β-cells led to vascular and endocrine cell disruption with a minor impairment in β-cell function. In contrast, expression of a soluble isoform of Vegf receptor 1 (sFlt1) in β-cells blocked the formation of the pancreatic vasculature and drastically stunted glucose response while islet architecture was not affected. Notably, these effects of dnVegfaa or sFlt1 were not observed in animals lacking vegfaa, vegfab, kdrl, kdr, or flt1 function, indicating that they interfere with multiple ligands and/or receptors. In adults, disrupted islet architecture persisted in dnVegfaa expressing animals, while sFlt1 expressing animals displayed large sheets of β-cells along their pancreatic ducts, accompanied by impaired glucose tolerance in both models. Thus, our study reveals novel roles for the vasculature in patterning and function of the islet.
Genes / Markers
Figures
Figure Gallery (4 images)
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Marker Marker Type Name
CreEFGCre
DsRedEFGDsRed
EGFPEFGEGFP
GAL4FFEFGGAL4FF
GCaMPEFGGCaMP
GFPEFGGFP
mCherryEFGmCherry
NTREFGNTR
RFPEFGRFP
TagBFPEFGTagBFP
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Citation
Mullapudi, S.T., Boezio, G.L.M., Rossi, A., Marass, M., Matsuoka, R.L., Matsuda, H., Helker, C.S.M., Yang, Y.H.C., Stainier, D.Y.R. (2019) Disruption of the pancreatic vasculature in zebrafish affects islet architecture and function. Development (Cambridge, England). 146(21):.