Endothelium-derived essential signals involved in pancreas organogenesis

Abstract

Endothelial cells (ECs) are essential for pancreas differentiation, endocrine specification, and endocrine function. They are also involved in the physiopathology of type 1 and type 2 diabetes. During embryogenesis, aortic ECs provide specific factors that maintain the expression of key genes for pancreas development such as pancreatic and duodenal homeobox-1. Other unknown factors are also important for pancreatic endocrine specification and formation of insulin-producing beta cells. Endocrine precursors proliferate interspersed with ductal cells and exocrine precursors and, at some point of development, these endocrine precursors migrate to pancreatic mesenchyme and start forming the islets of Langerhans. By the end of the gestation and close to birth, these islets contain immature beta cells with the capacity to express vascular endothelial growth factor and therefore to recruit ECs from the surrounding microenvironment. ECs in turn produce factors that are essential to maintain insulin secretion in pancreatic beta cells. Once assembled, a cross talk between endocrine cells and ECs maintain the integrity of islets toward an adequate function during the whole life of the adult individual. This review will focus in the EC role in the differentiation and maturation of pancreatic beta cells during embryogenesis as well as the current knowledge about the involvement of endothelium to derive pancreatic beta cells in vitro from mouse or human pluripotent stem cells.

Angiocrine functions of organ-specific endothelial cells

“…During the recuperation of islet cells from chemical injury, angiocrine signals drive regeneration of the pancreas and the resolution of diabetes 95, 96 . An angiocrine supply of BMP2 and BMP4 is crucial for islet-cell homeostasis 96 . Notably, the deposition of Laminin-α4 chain by ECs stimulates insulin production by islet cells 97 .…”

Notch Signaling in Pancreatic Development

“…The development of the pancreas depends on the spatio-temporal expression of a number of transcription factors and associated signaling pathways [ 63 , 64 ]. Studies on the transcriptional regulation of the pancreas have been reviewed extensively, and thus, not discussed in detail here.…”

Re-evaluating functional landscape of the cardiovascular system during development

“…Do our findings apply to other vertebrates such as mammals? In mice and frog, the critical importance of local interactions between vECs and developing organs have been shown for the development of liver and pancreas, respectively (Cleaver and Dor, 2012;Lammert et al, 2001Lammert et al, , 2003Talavera-Adame and Dafoe, 2015). Recently, an importance of vEC-tissue interactions is also implicated in liver organoid formation in vitro (Camp et al, 2017).…”