In vivo and in vitro techniques to study pancreas development and islet cell function.

ABSTRACT

Over the last decades, pancreas development has been widely investigated. Understanding the mechanisms that control beta-cell development should allow progress towards the regeneration of these cells in humans. Particularly, it is well established that inductive signals from the mesenchyme play an essential role in the proliferation of precursor cells. In the present review, we focused on the roles of fibroblast growth factors (FGFs) in pancreas development. Improvements of the in vivo and in vitro techniques were used to define the function of FGF10. Experiments on FGF10 knockout mice showed that FGF10 is required for the proliferation of precursor cells and the pancreas development. Several laboratories used different in vitro techniques to study the effect of FGF10 on beta-cell differentiation. These methods of investigation are described here. In our experiments, pancreases were placed at the air-liquid interface to define the precise mechanism of action of FGF10. We showed that FGF10 positively regulates the beta-cell mass by increasing the proliferation of the early precursors and by extending the window of expression of the endocrine precursor marker Ngn3. These data are compared with studies performed with other culture systems. Finally, the role of other FGFs is discussed.