INTEGRATED FGF AND BMP SIGNALING CONTROLS THE PROGRESSION OF PROGENITOR-CELL DIFFERENTIATION AND THE EMERGENCE OF PATTERN IN THE EMBRYONIC ANTERIOR-PITUITARY

The mechanisms by which inductive signals control the identity, prolif eration and timing of differentiation of progenitor cells in establish ing spatial pattern in developing vertebrate tissues remain poorly und erstood. We have addressed this issue in the embryonic anterior pituit ary, an organ in which distinct hormone cell types are generated in a precise temporal and spatial order from an apparently homogenous ectod ermal primordium. We provide evidence that in this tissue the coordina te control of progenitor cell identity, proliferation and differentiat ion is imposed by spatial and temporal restrictions in FGF- and BMP-me diated signals. These signals derive from adjacent neural and mesenchy mal signaling centers: the infundibulum and ventral juxtapituitary mes enchyme. The infundibulum appears to have a dual signaling function, s erving initially as a source of BMP4 and subsequently of FGF8. The ven tral juxtapituitary mesenchyme appears to serve as a later source of B MP2 and BMP7. In vitro, FGFs promote the proliferation of progenitor c ells, prevent their exit from the cell cycle and contribute to the spe cification of progenitor cell identity. BMPs, in contrast, have no app arent effect on cell proliferation but instead appear to act with FGFs to control the initial selection of thyrotroph and corticotroph proge nitor identity.