Fig. 2. Stages of pancreas development. Schematic cross-sections of developing embryos and organs, representing the progression of pancreas development. (A) Concomittant with specification of the organ, Pdx1 and Ptf1a initiate expression in two restricted domains of the gut endoderm (en). Nearby tissues, including notochord (nt) and aorta (ao), may promote this specification process (Kim et al., 1997; Lammert et al., 2001; Yoshitomi and Zaret, 2004). (B) Mesenchyme (mes) surrounds the thickening buds as the first Ngn3⁺ pro-endocrine cells appear. (C) Subsequent outgrowth produces a dense epithelial bud, in which early -cells begin to differentiate. (D) Further growth and branching precedes the secondary transition, which is marked by a massive differentiation of ß-cell and acinar cells, as well as by the progressive restriction of Pdx1 and Ptf1a expression to these respective cell types. (E) The organ has assumed its mature form by birth, with distinct islets of Langerhans scattered among exocrine acini and ducts.