Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding

• DOI: 10.1242/dev.098657
• Publication Date: 2014-02-27T04:09:34Z
• Authors: Rachel B. Reinert; Qing Cai; Ji-Young Hong; Jennifer L. Plank; Kristie Aamodt; Nripesh Prasad; Radhika Aramandla; Chunhua Dai; Shawn E. Levy; Ambra Pozzi; Patricia A. Labosky; Christopher V. E....; Marcela Brissova; Alvin C. Powers
• Keywords: Pancreatic Islets

Neurovascular alignment is a common anatomical feature of organs, but the mechanisms leading to this arrangement are incompletely understood. Here, we show that vascular endothelial growth factor (VEGF) signaling profoundly affects both vascularization and innervation pancreatic islet. In mature islets, nerves closely associated with capillaries, islet process during embryonic organogenesis significantly precedes innervation. Although simple neuronal meshwork interconnects developing clusters as they begin form at E14.5, substantial ingrowth nerve fibers into islets occurs postnatally, when already complete. Using genetic mouse models, demonstrate VEGF regulates indirectly through its effects on intra-islet cells. Our data indicate formation VEGF-directed, plexus required for development innervation, VEGF-induced hypervascularization leads increased fiber ingrowth. Transcriptome analysis hypervascularized revealed an expression extracellular matrix components axon guidance molecules, these transcripts being enriched in islet-derived cell population. We propose mechanism coordinated neurovascular within which endocrine cell-derived directs patterning capillaries embryogenesis, forming scaffold postnatal essential autonomic fibers.