Endocrine Pancreas Development and Regeneration: Noncanonical Ideas From Neural Stem Cell Biology
Loss of insulin-producing pancreatic islet b-cells is a hallmark of type 1 diabetes. Several experimental para- digms demonstrate that these cells can, in principle, be regenerated from multiple endogenous sources using signaling pathways that are also used during pancreas development. A thorough understanding of these path- ways will provide improved opportunities for therapeutic intervention. It is now appreciated that signaling path- ways should not be seen as “on” or “off” but that the degree of activity may result in wildly different cellular outcomes. In addition to the degree of operation of a signaling pathway, noncanonical branches also play im- portant roles. Thus, a pathway, once considered as “off” or “low” may actually be highly operational but may be using noncanonical branches. Such branches are only now revealing themselves as new tools to assay them are being generated. A formidable source of noncanon- ical signal transduction concepts is neural stem cells because these cells appear to have acquired unusual signaling interpretations to allow them to maintain their unique dual properties (self-renewal and multipotency). We discuss how such findings from the neural field can provide a blueprint for the identification of new molec- ular mechanisms regulating pancreatic biology, with a focus on Notch, Hes/Hey, and hedgehog pathways.
Jimmy Masjkur, Steven W. Poser, Polyxeni Nikolakopoulou, George Chrousos, Ronald D. McKay, Stefan R. Bornstein, Peter M. Jones, and Andreas Androutsellis-Theotokis.
Diabetes. 2016 Feb;65(2):314-30. doi: 10.2337/db15-1099.