Altered expression of PTH type-2 receptor and TIP39

PTH 2 型受体和 TIP39 表达改变

• 批准号: 6953844
• 负责人: DAVID Alan RUBIN
• 金额: $ 21万
• 依托单位: ILLINOIS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-09 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6953844
• 关键词: brain morphology; cell differentiation; developmental genetics; developmental neurobiology; genetic markers; genetically modified animals; hormone receptor; in situ hybridization; neuroendocrine system; neurogenesis; parathyroid hormones; protein localization; receptor expression; vertebrate embryology; zebrafish

DESCRIPTION (provided by applicant): Tuberoinfundibular peptide 39 (TIP39) and Parathyroid Hormone (PTH) type-2 receptor (PTH2R) constitute a new endocrine system with conserved neuronal mRNA expression in zebrafish and mouse brain. The functions associated with the murine TIP39-PTH2R system include nociception and regulation of hypothalamic (GnRH) and pituitary hormones (ACTH, GH, and LH). Zebrafish studies have shown that TIP39 and the PTH2R are expressed early in brain development in a spatial and temporal relationship with sonic hedgehog (Shh). Furthermore, embryos which have TIR39 expression inhibited by morpholino are not viable and show severely impaired brain development. Thus, the zebrafish TIP39-PTH2R studies suggest that this system serves a crucial role in neuroendocrine development and perhaps other organs such as pancreas and heart where TIR39 and the PTH2R are expressed. Therefore, the zebrafish, Danio rerio, provides a powerful model system to study TIR39-PTH2R-regulated mechanisms during development of the central nervous system (CNS). Hence, molecular analyses are proposed to better elucidate the effects of altered zebrafish PTH2R and TIR39 transcript expression during early brain development. Three aims will be pursued, 1) Evaluation of PTH2R and TIP39 MO-injected embryos during early brain development by examining the expression of Shh, GH, ACTH, LH, and GnRH. 2) Determine the relationship between TIP39 and Shh during brain development by examining the locale of cells expressing TIP39 in embryos which have a deficiency for Shh or Shh signaling (sonic you and slow-muscle-omitted). 3) Evaluation of PTH2R and TIP39 overexpression in the brain and hypothalamus (respectively) during early brain development by examining the expression of the marker genes described above. Because the PTH2R has not been analyzed by gene knockout in any organism, these experiments will provide novel insights into the role of this new TIP39-PTH2R system in normal and perturbed embryos. This work is part of a long-term molecular developmental-genetic investigation on the mechanistic role(s) of TIP39-PTH2R system during CNS, and other organ, development.

描述（由申请人提供）：在斑马鱼和小鼠脑中，垂体漏斗肽39（TIP 39）和甲状旁腺激素（PTH）2型受体（PTH 2 R）构成了一种新的内分泌系统，具有保守的神经元mRNA表达。与鼠TIP 39-PTH 2 R系统相关的功能包括伤害感受和下丘脑（GnRH）和垂体激素（ACTH、GH和LH）的调节。斑马鱼的研究表明，TIP 39和PTH 2 R在大脑发育的早期表达，与音刺猬（Shh）存在空间和时间关系。此外，具有被吗啉代抑制的TIR 39表达的胚胎不能存活，并且显示出严重受损的脑发育。因此，斑马鱼TIP 39-PTH 2 R研究表明，该系统在神经内分泌发育中起着至关重要的作用，可能还包括其他器官，如胰腺和心脏，其中TIR 39和PTH 2 R表达。因此，斑马鱼，Danio rerio，提供了一个强大的模型系统来研究TIR 39-PTH 2 R调控机制在中枢神经系统（CNS）的发展。因此，分子分析提出了更好地阐明改变斑马鱼PTH 2 R和TIR 39转录表达在早期脑发育过程中的影响。1）通过检测Shh、GH、ACTH、LH和GnRH的表达来评价在早期脑发育期间注射PTH 2 R和TIP 39 MO的胚胎。2)通过检查胚胎中表达TIP 39的细胞的位置来确定TIP 39和Shh在大脑发育过程中的关系，这些胚胎缺乏Shh或Shh信号（sonic you和slow-muscle-省略）。3)通过检查上述标记基因的表达，评价在早期脑发育过程中脑和下丘脑中PTH 2 R和TIP 39（分别）的过表达。由于PTH 2 R尚未在任何生物体中通过基因敲除进行分析，因此这些实验将为这种新的TIP 39-PTH 2 R系统在正常和受干扰胚胎中的作用提供新的见解。这项工作是对TIP 39-PTH 2 R系统在CNS和其他器官发育过程中的机制作用进行长期分子发育遗传学研究的一部分。