Vascular instruction of pancreas development

Abstract

SummaryBlood vessels course through organs, providing them with essential nutrient and gaseous exchange. However, the vasculature has also been shown to provide non-nutritional signals that play key roles in the control of organ growth, morphogenesis and homeostasis. Here, we examine a decade of work on the contribution of vascular paracrine signals to developing tissues, with a focus on pancreatic -cells. During the early stages of embryonic development, blood vessels are required for pancreas specification. Later, the vasculature constrains pancreas branching, differentiation and growth. During adult life, capillaries provide a vascular niche for the maintenance of -cell function and survival. We explore the possibility that the vasculature constitutes a dynamic and regionalized signaling system that carries out multiple and changing functions as it coordinately grows with the pancreatic epithelial tree.

Hypoglycemia Reduces Vascular Endothelial Growth Factor A Production by Pancreatic Beta Cells as a Regulator of Beta Cell Mass

“…VEGF-A expression by beta cells has been shown to be important for proper pancreatic organogenesis and proper insulin secretion (1,2,6,19,20). However, most rodent studies on VEGF-A in beta cells were based on either gene deletion or on overexpression under a strong promoter in beta cells (7,19,23).…”

Short-term overexpression of VEGF-A in mouse beta cells indirectly stimulates their proliferation and protects against diabetes

“…Nevertheless, evidence accumulates for the importance of vascular-derived signals in development and function of the endocrine pancreas [1][2][3][4][5][6][7][8], reviewed in [9]. Although the exact nature of the inductive signals is at present unknown, cell-cell contact with the endothelium is responsible for proper pancreatic development [1].…”

The anterior chamber of the eye is a transplantation site that supports and enables visualisation of beta cell development in mice

“…The differentiation process within the ACE may be facilitated by the rapid revascularisation of the graft, which seems to be completed by PTD-10. A three-dimensional reconstruction of these blood vessels shows that, similar to the native pancreas, there is a high density of fine blood vessels in the isletlike endocrine clusters of the pancreas which supply the islet cells with nutrients and growth factors necessary for islet development [9]. With appropriate reporter constructs and transgenic lines, this transplantation model provides a unique opportunity to study and identify factors regulating development of the endocrine pancreas in vivo, in real time.…”