Figure 9. Multiple roles for dmrt5 in pituitary differentiation.

A, Model for dmrt5 function in corticotrope vs gonadotrope differentiation. In wild-type embryos (top panel), dmrt5 expression is restricted to the aPD and regulates corticotrope differentiation from bipotential precursors via regulation of tbx19 expression. The pPD lacks dmrt5 expression and gonadotrope differentiation is not inhibited by Tbx19. In dmrt5 mutants and morphants (bottom panel), absence of Tbx19 mediated repression results in gonadotrope formation also in the aPD. B, Model for dmrt5 role in lactotrope maintenance and positioning. Wild-type embryos (top panel) show tight clustering of corticotropes and lactotropes in aPD, gonadotropes, thyrotropes, and somatotropes in pPD and melanotropes in PI. In dmrt5 morphants and mutants, anterior pituitary precursor cells fail to differentiate into corticotropes. As a result, lactotropes, usually closely linked to corticotropes, become scattered throughout the pituitary. They eventually enter apoptosis after initially normal differentiation. Note that melanotropes in PI as well as somatotropes and thyrotropes (not shown) are not affected.