Hedgehog Signaling Patterns the Zebrafish Pituitary

描述(由申请人提供)：这项提案将研究刺猬(HH)信号在斑马鱼脑下垂体发育中的作用。脑下垂体在脊椎动物中产生七种主要激素，影响重要的生理功能，如生长调节、生殖功能和免疫反应。人类垂体发育缺陷，如垂体腺功能减退，影响了大量儿童，并导致包括生长激素缺乏症(GHD)在内的各种发育问题。甲状旁腺功能减退症是一系列综合征(全前脑、Pallister-Hall)的一部分，与HH信号的缺陷有关，HH信号是一种高度保守的信号通路。利用斑马鱼的遗传学，我们已经证明了HH信号是正常脑垂体发育所必需的。我们的数据显示，HH信号在诱导、模式形成和维持三个阶段影响斑马鱼脑下垂体的发育。该项目的目的是利用可获得的斑马鱼胚胎构建一个精确的图谱，定义垂体腺在形成过程中的不同区域特征，描述HH信号缺陷如何导致不同的垂体腺缺陷，并了解某些细胞类型何时需要HH信号才能分化为激素分泌细胞。斑马鱼HH突变体为剖析HH信号在脑垂体发育中所起的各种关键作用提供了独特的资源。这项研究应该与影响脑下垂体的人类发育缺陷直接相关。

DESCRIPTION (provided by applicant): 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.