Re-expression of the pro-endocrine factor Ngn3 in the pancreatic ductal lining upon α-cell-specific <i>Arx</i> loss.

(A–F) The investigation of the expression of the pro-endocrine marker Ngn3 in animals as old as 13 month-old Glu-ArxKO animals revealed its re-expression in the ductal lining of mutant animals (B–C, E–F), while being absent or very weakly expressed in their control counterparts (A, D). (G–I) A time course analysis of Dox+ IndGlu-ArxKO pancreata from animals treated with Dox for increasing durations outlined Ngn3+ cells within the ductal epithelium (H inlet) and lining (H), as well as in islet cells adjacent to ducts, as early as 10 days post Dox treatment initiation (H compared to G). A similar trend was also noted 11 days later (I). The downstream target of Ngn3, Rfx6, classically labeling endocrine cells (J), appeared additionally ectopically expressed in the ductal lining of 13 month-old Glu-ArxKO animals (K–L - arrowheads outline a few examples). Note that D–F photographs correspond to blowups of A–C. For the purpose of clarity, in selected photographs, islets are outlined in dashed yellow/black lines while the ductal lumen is outlined in white lines (D: ductal lumen).