Fig. 6. Model of endocrine subtype specification during pancreatic development. (A) An endocrine precursor cell initially expresses both Arx and Pax4, most probably in an inactive form. In a first round of competitive fate allocation, an unknown factor determines which factor will predominate: if it is Arx, the -cell fate will be specified (with Arx inhibiting Pax4 expression), whereas Pax4 will induce ß-/-cell lineages through the inhibition of Arx transcription (1). In the case of Pax4 prevalence, the resulting ß-/-cell precursor is poised to undergo a second round of fate allocation (2). In this second event, Pax4 seemingly induces the ß-cell fate at the expense of the -cell lineage. A hypothetical `factor X' is envisioned to have an opposite function, promoting the -cell fate to the detriment of ß-cell specification (3). (B-D) Fate changes in the case of Arx (B), Pax4 (C), or combined Arx/Pax4 (D) deficiency. See main text for details. For the purpose of simplification, exocrine cell and PP-cell development are not represented.