Hedgehog Signaling Patterns the Zebrafish Pituitary

描述（由申请人提供）：本提案将研究刺猬（Hh）信号在斑马鱼脑垂体发育中的作用。脑下垂体在脊椎动物中产生七种主要激素，这些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。人类垂体发育的缺陷，如垂体功能减退症，影响了大量的儿童，并导致各种发育问题，包括生长激素缺乏症（GHD）。垂体功能减退症是许多综合征（前脑无裂，Pallister-Hall）的一部分，这些综合征与Hh信号传导（一种高度保守的信号传导途径）的缺陷有关。使用斑马鱼遗传学，我们已经表明Hh信号是正常垂体发育所必需的。我们的数据表明，Hh信号影响斑马鱼垂体发育的三个阶段：诱导，patteming，和维护。该项目的目的是使用可访问的斑马鱼胚胎来构建一个精确的地图，定义垂体中不同的区域身份，因为它们正在形成，以表征Hh信号缺陷如何导致不同的垂体缺陷，并了解某些细胞类型何时需要Hh信号，以分化为激素分泌细胞。斑马鱼Hh突变体为解剖Hh信号在垂体发育中的各种关键作用提供了独特的资源。这项工作应该与影响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.