Guner, B., Ozacar, A.T., Thomas, J.E., and Karlstrom, R.O. (2008) Graded hedgehog and fibroblast growth factor signaling independently regulate pituitary cell fates and help establish the pars distalis and pars intermedia of the zebrafish adenohypophysis. Endocrinology. 149(9):4435-4451.
The vertebrate adenohypophysis forms as a placode at the anterior margin of the neural plate, requiring both Hedgehog (Hh) and Fibroblast growth factor (Fgf) mediated cell-cell signaling for induction and survival of endocrine cell types. Using small molecule inhibitors to modulate signaling levels during zebrafish development we show that graded Hh and Fgf signaling independently help establish the two sub-domains of the adenohypophysis, the anteriorly located Pars Distalis (PD) and the posterior Pars Intermedia (PI). High levels of Hh signaling are required for formation of the PD and for differentiation of anterior endocrine cell types, while lower levels of Hh signaling are required for formation of the PI and differentiation of posterior endocrine cell types. In contrast, high Fgf signaling levels are required for formation of the PI and for posterior endocrine cell differentiation, while anterior regions require lower levels of Fgf signaling. Based on live observations and marker analyses we show that the PD forms first at the midline closest to the CNS source of Shh. In contrast the PI appears to form from more lateral/posterior cells close to a CNS source of Fgf3. Together our data show that graded Hh and Fgf signaling independently direct induction of the PD and PI and help establish endocrine cell fates along the anterior/posterior axis of the zebrafish adenohypophysis. These data suggest that there are distinct origins and signaling requirements for the PD and PI.