This proposal will examine the role of hedgehog (Hh) signaling in zebrafish pituitary development. The pituitary gland produces seven major hormones in vertebrates that influence vital physiological functions such as regulation of growth, reproductive function, and immune response. Defects in human pituitary development such as hypopituitarism affect a large number of children and are responsible for a variety of developmental problems including growth hormone deficiencies (GHD). Hypopituitarism is part of a number of syndromes (Holoprosencephaly, Pallister-Hall), that have been linked to defects in Hh signaling, a highly conserved signaling pathway. Using zebrafish genetics, we have shown Hh signaling is required for normal pituitary development. Our data shows Hh signaling influences zebrafish pituitary development during three phases: induction, patteming, and maintenance.
The aims of this project are to use the accessible zebrafish embryo to construct a precise map defining different regional identities in the pituitary as they are forming, to characterize how defects in Hh signaling lead to different pituitary defects, and to understand when certain cell types need Hh signaling in order to differentiate as hormone secreting cells. The zebrafish Hh mutants provide a unique resource for dissecting the varied and critical roles Hh signaling plays in pituitary development. This work should relate directly to human developmental defects that affect the pituitary.
