Hedgehog Signaling Patterns the Zebrafish Pituitary

描述（由申请人提供）：本提案将研究刺猬（Hh）信号在斑马鱼垂体发育中的作用。脊椎动物的脑下垂体产生七种主要激素，影响重要的生理功能，如生长调节、生殖功能和免疫反应。垂体功能低下等人类垂体发育缺陷影响了大量儿童，并导致了包括生长激素缺乏症（GHD）在内的各种发育问题。垂体功能减退症是许多综合征（前脑畸形，palliter - hall）的一部分，这些综合征与Hh信号通路的缺陷有关，Hh信号通路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Hh信号是正常垂体发育所必需的。我们的数据显示Hh信号影响斑马鱼垂体发育的三个阶段：诱导、模式和维持。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地图，定义垂体形成过程中的不同区域身份，表征Hh信号缺陷如何导致不同的垂体缺陷，并了解某些类型的细胞何时需要Hh信号才能分化为激素分泌细胞。斑马鱼Hh突变体为解剖Hh信号在垂体发育中发挥的各种关键作用提供了独特的资源。这项工作应该与影响脑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.