RRC ID 66028
Author Mullapudi ST, Boezio GLM, Rossi A, Marass M, Matsuoka RL, Matsuda H, Helker CSM, Yang YHC, Stainier DYR.
Title Disruption of the pancreatic vasculature in zebrafish affects islet architecture and function.
Journal 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, although 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, whereas 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.
Volume 146(21)
Published 2019-11-4
DOI 10.1242/dev.173674
PII dev.173674
PMID 31597659
MeSH Animals Blood Glucose / analysis Gene Expression Regulation, Developmental Glucose / metabolism Glucose Tolerance Test Green Fluorescent Proteins / metabolism Islets of Langerhans / cytology* Ligands Microscopy, Fluorescence Mutation Pancreas / blood supply* Pancreas / embryology Transgenes Vascular Endothelial Growth Factor A / metabolism Vascular Endothelial Growth Factor Receptor-1 / metabolism Zebrafish Zebrafish Proteins / metabolism
IF 5.611
Zebrafish TgBAC(pdgfrb:EGFP)ncv22Tg