Little is known about the extracellular signals that drive beta cell specification from Ngn3 + progenitors. Animals lacking Nkx6.1 and Nkx2.2 have defects in beta cell formation. MafA has also been implicated in the terminal differentiation of beta cells, particularly in the beta cell-specific reactivation of Pdx1. However, several observations point to Pax4 as the main hallmark of beta cell differentiation: The knockout of this gene results in the total absence of beta cells, but not alpha cells; its expression peaks between e13.5 and e15.5, which coincides with the period of maximal differentiation of beta cell precursors ; and shortly after endocrine specification, Ngn3 colocalizes with Pax4 , which suggests that the latter may be one of the targets of the former. Read the rest of this entry »