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）：结核菌肽39（TIP39）和甲状旁腺激素（PTH）型2受体（PTH2R）构成了一种新的内分泌系统，具有保守的神经元mRNA在斑马鱼和小鼠脑中。与鼠TIP39-PTH2R系统相关的功能包括下丘脑（GNRH）和垂体激素（ACTH，GH和LH）的伤害感受和调节。斑马鱼的研究表明，TIP39和PTH2R在与Sonic刺猬（SHH）的空间和时间关系中在大脑发育的早期表达。此外，具有TIR39表达的胚胎被形态抑制是不可行的，并且显示出严重受损的脑发育。因此，斑马鱼TIP39-PTH2R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，也许在表达TiR39和PTH2R的其他器官（例如胰腺和心脏）中起着至关重要的作用。因此，斑马鱼Danio Rerio提供了一个强大的模型系统，可以在中枢神经系统（CNS）开发过程中研究TIR39-PTH2R调节的机制。因此，提出了分子分析，以更好地阐明在早期大脑发育过程中斑马鱼PTH2R和TIR39转录本表达改变的影响。将追求三个目标，1）通过检查SHH，GH，ACTH，LH和GNRH的表达，在早期大脑发育过程中对PTH2R和TIP39 MO注射的胚胎进行评估。 2）通过检查在胚胎中表达tip39的细胞的位置来确定tip39和SHH之间的关系，这些细胞在胚胎中表达tip39，而胚胎的SHH或SHH信号传导不足（Sonic You and Slow-Muscle-of-of）。 3）在早期大脑发育过程中，通过检查上述标记基因的表达来评估大脑和下丘脑中PTH2R和TIP39的过表达。由于尚未通过任何生物体中的基因敲除对PTH2R进行分析，因此这些实验将为这种新的TIP39-PTH2R系统在正常和扰动的胚胎中的作用提供新的见解。这项工作是对CNS和其他器官开发过程中TIP39-PTH2R系统机械作用的长期分子发育遗传学研究的一部分。