Historical Perspective: Beginnings of the β-Cell

Over the course of the last half-century, we have gleaned much about the developmental biology of the pancreas and in particular the insulin-producing β-cell, the autoimmune destruction of which results in type 1 diabetes. Deciphering the mechanisms driving β-cell neogenesis in vivo holds great allure, in large part because of the potential therapeutic applications that stand to be gained. The field of pancreas development was arguably established by such scientists as Rutter, Grobstein, Wessells, and Cohen in the 1960s. Their seminal studies were the first to demonstrate the significance of the mesenchyme in supporting development of the pancreas or indeed any organ. Their work was further extended by Teitelman and colleagues who did much to characterize pancreatic differentiation via immunohistochemistry. Over the last two decades, the emergence of increasingly elaborate knockout and transgenic mouse technologies has exponentially expanded our insight into the signaling pathways and transcriptional nexus governing pancreas development. Thus, it is fitting that this review will mainly focus on the development of the pancreas and β-cells in the mouse. Through recapitulating endogenous signaling pathways governing β-cell neogenesis in the embryo, it has recently proven possible to generate insulin-producing cells in vitro from human embryonic stem cells (hESCs) (1). Although this milestone accentuates the great therapeutic potential of studying β-cell neogenesis in vivo, the currently insufficient functionality of hESC-derived insulin cells argues the case for further examination of β-cell development in order to understand how and why such engineered cells differ from their endogenous counterparts. It is likely that resolving these differences will lie in better characterizing the relationships between the many signaling pathways and key factors already known to govern the pancreatic program in regards to spatial and temporal pancreatic expression and their impact on pancreatic differentiation. It is envisaged that such incremental knowledge gains will be applied …