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.

Keywords: Endothelium; Endothelium-derived signals; Differentiation; Pancreas development; Organogenesis

Core tip: Many studies have demonstrated that endothelial cells (ECs) have an important role in organogenesis. For instance, during embryogenesis, aortic ECs provide specific factors that maintain the expression of key genes for pancreas development. Other unknown factors are also important for pancreatic endocrine specification and formation of insulin-producing beta cells. In addition, by the end of the gestation and close to birth, pancreatic islets contain immature beta cells with the capacity to express factors that recruit ECs from the surrounding microenvironment and form a functional unit that will lasts for the whole life of the individual. In the present review, we will analyze the current endothelial-derived factors called angiocrine factors that are essential in organogenesis and we will focus the role of these factors in pancreas development and pancreatic beta cells.