Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding

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 of the pancreatic islet. In mat...

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Veröffentlicht in:Development (Cambridge) 2014-04, Vol.141 (7), p.1480-1491
Hauptverfasser: Reinert, Rachel B, Cai, Qing, Hong, Ji-Young, Plank, Jennifer L, Aamodt, Kristie, Prasad, Nripesh, Aramandla, Radhika, Dai, Chunhua, Levy, Shawn E, Pozzi, Ambra, Labosky, Patricia A, Wright, Christopher V E, Brissova, Marcela, Powers, Alvin C
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container_end_page 1491
container_issue 7
container_start_page 1480
container_title Development (Cambridge)
container_volume 141
creator Reinert, Rachel B
Cai, Qing
Hong, Ji-Young
Plank, Jennifer L
Aamodt, Kristie
Prasad, Nripesh
Aramandla, Radhika
Dai, Chunhua
Levy, Shawn E
Pozzi, Ambra
Labosky, Patricia A
Wright, Christopher V E
Brissova, Marcela
Powers, Alvin C
description 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 of the pancreatic islet. In mature islets, nerves are closely associated with capillaries, but the islet vascularization process during embryonic organogenesis significantly precedes islet innervation. Although a simple neuronal meshwork interconnects the developing islet clusters as they begin to form at E14.5, the substantial ingrowth of nerve fibers into islets occurs postnatally, when islet vascularization is already complete. Using genetic mouse models, we demonstrate that VEGF regulates islet innervation indirectly through its effects on intra-islet endothelial cells. Our data indicate that formation of a VEGF-directed, intra-islet vascular plexus is required for development of islet innervation, and that VEGF-induced islet hypervascularization leads to increased nerve fiber ingrowth. Transcriptome analysis of hypervascularized islets revealed an increased expression of extracellular matrix components and axon guidance molecules, with these transcripts being enriched in the islet-derived endothelial cell population. We propose a mechanism for coordinated neurovascular development within pancreatic islets, in which endocrine cell-derived VEGF directs the patterning of intra-islet capillaries during embryogenesis, forming a scaffold for the postnatal ingrowth of essential autonomic nerve fibers.
doi_str_mv 10.1242/dev.098657
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Here, we show that vascular endothelial growth factor (VEGF) signaling profoundly affects both vascularization and innervation of the pancreatic islet. In mature islets, nerves are closely associated with capillaries, but the islet vascularization process during embryonic organogenesis significantly precedes islet innervation. Although a simple neuronal meshwork interconnects the developing islet clusters as they begin to form at E14.5, the substantial ingrowth of nerve fibers into islets occurs postnatally, when islet vascularization is already complete. Using genetic mouse models, we demonstrate that VEGF regulates islet innervation indirectly through its effects on intra-islet endothelial cells. Our data indicate that formation of a VEGF-directed, intra-islet vascular plexus is required for development of islet innervation, and that VEGF-induced islet hypervascularization leads to increased nerve fiber ingrowth. Transcriptome analysis of hypervascularized islets revealed an increased expression of extracellular matrix components and axon guidance molecules, with these transcripts being enriched in the islet-derived endothelial cell population. 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Transcriptome analysis of hypervascularized islets revealed an increased expression of extracellular matrix components and axon guidance molecules, with these transcripts being enriched in the islet-derived endothelial cell population. We propose a mechanism for coordinated neurovascular development within pancreatic islets, in which endocrine cell-derived VEGF directs the patterning of intra-islet capillaries during embryogenesis, forming a scaffold for the postnatal ingrowth of essential autonomic nerve fibers.</abstract><cop>England</cop><pub>Company of Biologists</pub><pmid>24574008</pmid><doi>10.1242/dev.098657</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Blood Vessels - embryology
Blood Vessels - physiology
Cell Communication - genetics
Cells, Cultured
Embryo, Mammalian
Endothelium, Vascular - embryology
Endothelium, Vascular - metabolism
Endothelium, Vascular - physiology
Female
Islets of Langerhans - blood supply
Islets of Langerhans - embryology
Islets of Langerhans - innervation
Mice
Mice, Transgenic
Neovascularization, Physiologic - physiology
Vascular Endothelial Growth Factor A - genetics
Vascular Endothelial Growth Factor A - physiology
title Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding
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