THE ROLE(S) OF FRZB CHICK SOMITE PATTERNING

FRZB 鸡体节模式的作用

• 批准号: 2842804
• 负责人: Laura W. Burrus
• 金额: $ 10.02万
• 依托单位: SAN FRANCISCO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-08 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2842804
• 关键词: cartilage development; chick embryo; complementary DNA; developmental genetics; fibroblast growth factor; gene expression; growth factor; myogenesis; neurogenesis; nonmammalian vertebrate embryology; pluripotent stem cells; soma; transfection /expression vector

DESCRIPTION (adapted from investigator's abstract): The development of a vertebrate organism from a single fertilized egg is a complex series of events involving both cell proliferation and specialization. Many of these events have been shown to be mediated by intercellular signals. To date, four families of secreted proteins that provide essential intercellular cues during development have been identified. These include the fibroblast growth factor (FGF) family, the hedgehog (Hh) family, the transforming growth factors (TGF-B) family, and the Wnt family. These protein families are involved in a variety of developmental processes and their mode of action has been highly conserved throughout evolution. The overall goal of this project is to understand the role(s) of these signals in directing chick somite cells to develop into either muscle, bone, or skin. Although these somite cells are initially pluripotential, cells located dorsally are instructed to become skeletal muscle whereas cells that are located ventrally are instructed to become axial skeleton (for review, see Christ and Ordahl, 1995). Wnt proteins are secreted signaling factors that have been shown to have opposing roles in inducing myogenesis and in repressing chondrogenesis (Munsterberg et al, 1995; Rudnicki and Brown, 1997; Capdevila et al, 1998). Recently, an antagonist of Wnt activity, called frzb, has been identified in a number of species (for review, see Moon et al, 1997). In the mouse,fab-1 is expressed in segmental plate and newly formed somites (Leyns et al, 1997), suggesting the exciting possibility that it may function as a negative regulator of Wnt activity in developing somites. The experiments described in this proposal are designed to answer some important questions pertaining to somite patterning. First, is there a chick homologue of frzb that is also expressed in segmental plate and/or somites? if so, does frzb act to inhibit myogenesis and/or promote chondrogenesis in developing somites? As we acquire a better understanding of the molecular cues required for skeletal muscle and bone specification, we will be paving the way for the development of techniques by which diseased or injured muscle tissue and/or bone can be regenerated. In addition, by establishing these types of interactions between signaling molecules, we are not only enhancing our knowledge of how muscle tissue is generated during normal development; we are also identifying regulatory motifs that may play a role in a variety of other developmental processes as well as cancer.

描述（改编自研究者摘要）： 脊椎动物从一个受精卵发育成一个有机体是一系列复杂的过程 涉及细胞增殖和特化。其中许多事件 被证明是由细胞间信号介导的。迄今为止， 在发育过程中提供基本细胞间信号的分泌蛋白 已被确认。这些包括成纤维细胞生长因子（FGF）家族， hedgehog（Hh）家族、转化生长因子（TGF-B）家族，以及 Wnt家族这些蛋白质家族参与了多种 发育过程及其作用方式高度保守 在整个进化过程中。本项目的总体目标是了解 这些信号在引导鸡体节细胞发育成 肌肉、骨骼或皮肤。虽然这些体节细胞最初 位于背侧的多能细胞被指示成为骨骼肌 而位于腹侧的细胞则被指示成为轴向细胞， 骨架（综述见Christ和Ordahl，1995年）。Wnt蛋白是分泌的 已被证明在诱导中具有相反作用的信号传导因子 肌生成和抑制软骨形成（Munsterberg等，1995; Rudnicki 和Brown，1997; Capdevila等人，1998）。最近，Wnt拮抗剂 已经在许多物种中鉴定了称为FRZB的活性（为了回顾， 参见Moon等人，1997）。在小鼠中，fab-1在节段板中表达， 新形成的体节（Leyns et al，1997），提示了令人兴奋的可能性 它可能在发育过程中作为Wnt活性的负调节剂发挥作用， 体节本提案中描述的实验旨在回答一些问题。 关于体节模式的重要问题。首先，有没有一只小鸡 frzb的同源物也在节板和/或体节中表达？如果 那么，frzb是否起到抑制肌生成和/或促进软骨生成的作用， 发育体节？当我们对分子线索有了更好的理解 骨骼肌和骨骼规格所需的，我们将铺平道路 用于开发一种技术， 和/或骨可以再生。此外，通过建立这些类型 信号分子之间的相互作用，我们不仅增强了我们的 了解肌肉组织在正常发育过程中是如何产生的;我们 还鉴定了可能在多种其他生物学行为中起作用的调控基序， 发育过程以及癌症。