Role of BMP and FGF signaling during limb development

BMP 和 FGF 信号在肢体发育过程中的作用

• 批准号: 7061012
• 负责人: MARK B LEWANDOSKI
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7061012
• 关键词: apoptosis; biological signal transduction; bone development; bone morphogenetic proteins; cell line; developmental genetics; ectoderm; fibroblast growth factor; gene expression; gene induction /repression; growth factor receptors; limbs; mesenchyme; receptor expression; recombinase

We are studying the inter-relationship between FGF and BMP signaling. Limb development is ideal for such studies because of the wealth of information describing the genetic pathways and signaling molecules that pattern the three axis of the limb. Current models of limb development suggest that BMP signaling plays a role in controlling the normal cell death that occurs in mesenchymal interdigit cells, sculpting the final digit pattern, but the exact role of BMPs in this process are unknown. By simultaneously inactivating the Bmp receptor gene, Bmpr1a as well as Fgf8 and Fgf4 specifically in the limb bud ectoderm, we have produced genetic evidence for a novel model in which the surface ectoderm must receive a BMP signal, resulting in down regulation of FGFs which in turn induces apoptosis of the underlying mesenchyme. Thus both BMPs and FGF cooperate to control the essential cell function of programmed cell death. We are extending these studies by studying the role of BMP and FGF signaling in various aspects of limb development using mouse lines that express Cre in specific region of the developing limb.

我们正在研究 FGF 和 BMP 信号传导之间的相互关系。肢体发育是此类研究的理想选择，因为有大量信息描述了构成肢体三轴的遗传途径和信号分子。目前的肢体发育模型表明，BMP 信号传导在控制间充质指间细胞中发生的正常细胞死亡、塑造最终的手指模式方面发挥着重要作用，但 BMP 在此过程中的确切作用尚不清楚。通过同时灭活肢芽外胚层中的 Bmp 受体基因 Bmpr1a 以及 Fgf8 和 Fgf4，我们为一种新模型提供了遗传证据，其中表面外胚层必须接收 BMP 信号，导致 FGF 下调，进而诱导底层间充质细胞凋亡。因此，BMP 和 FGF 共同控制程序性细胞死亡的基本细胞功能。我们正在扩展这些研究，使用在发育肢体特定区域表达 Cre 的小鼠系来研究 BMP 和 FGF 信号传导在肢体发育各个方面的作用。