Multiple roles for hedgehog signaling in zebrafish pituitary development
Hedgehog (Hh) signaling is required in many developmental processes including overall growth, induction of various cell types and morphogenesis. One of the earliest discoveries regarding Hh signaling was its role as a morphogen in the spinal cord. Hh expression in the adjacent notochord and in the floor plate result in the induction of ventral cell types in a dose-dependent manner based on their distance from these sources of Hh. The downstream transcription factors, the Gli proteins, mediate the transcriptional response to Hh signaling. The functions of the three vertebrate Glis diverge somewhat among species and appear to be both temporally regulated and tissue specific. The first goal of my dissertation was to examine whether Hh was necessary and sufficient for proper pituitary development in zebrafish. I used a combination of genetic analysis, overexpression, and a pharmacological blocking agent and discovered that Hh signaling is not only required for pituitary development but is also capable of inducing ectopic secretory cells outside of the pituitary. I was also able to define precisely when Hh signaling is required for induction and patterning of the pituitary. The second goal of my dissertation was to illuminate the roles of the Gli proteins in transducing Hh signaling in pituitary development. Additional genetic analysis as well as temporally regulated knockdowns of each Gli protein have unveiled both overlapping and distinct functions for the Glis. During early development, both Gli1 and Gli2 have activator roles and are necessary for proper induction of the pituitary and for the Hh response in the pituitary. Later, Gli1 remains a Hh-dependent activator of the pituitary while the role of Gli2 changes to that of a repressor. Removal of the Gli2 repressor function results in transfating of pituitary cells such that normally anterior cell types differentiate in the posterior at the expense of existing posterior cell types. My analyses, therefore, have uncovered multiple roles for Hh signaling in pituitary development as well as both overlapping and divergent functions for the Glis in a manner that is temporally regulated.