Control of muscle precursor cell migration by inductive and cell autonomous signals

通过诱导和细胞自主信号控制肌肉前体细胞迁移

• 批准号: 5106086
• 负责人: Professor Dr. Thomas Braun
• 金额: --
• 依托单位: Abteilung I: Entwicklung und Umbau des Herzens
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 1998
• 资助国家: 德国
• 起止时间: 1997-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5106086?language=en
• 关键词: Control; muscle; precursor; cell; migration

In the last application we have shown that the homeobox gene Lbx1 determines the migratory routes of muscle precursor cells in a cell autonomous manner. Our results demonstrated that Lbx1 is a key regulator of muscle precursor cell migration and required for targeted migration of precursor cells of hind limb muscles and extensor muscle of forelimbs. Ectopic expression of Lbx1 induced expression of muscle cell markers indicating that Lbx1 may have a dual role in controlling both the migration behavior of muscle precursor cells and the determination of their fate. Furthermore, we have unveiled a role of shh in the maintenance of hypaxial muscle cells and the formation of specific muscle groups derived from migratory precursor cells. In the next period we will investigate how Lbx1 specifies the migration path of subsets of limb muscle precursor cells. In particular, we will isolate heterozygous and homozygous Lbx1 expressing cells using the knocked-in LacZ gene and identify putative target genes of Lbx1. The contribution of cell autonomous information for targeted cell migration will be analyzed in xenotransplants of somites from heterozygous and homozygous mice into chicken host embryos. In addition, we will continue our efforts to characterize the role of secreted and membranebound molecules to direct migration of limb bud precursor cells. We will also generate double homozygous Lbx1/Mox2 and Lbx1/Pitx1 mutant mice to analyze compensatory regulatory pathways and differences in the migration of cells toward fore limb and hind limb.

在最后的应用中，我们已经表明，同源异型盒基因Lbx 1决定了肌肉前体细胞在细胞自主的方式迁移路线。我们的研究结果表明，Lbx 1是肌肉前体细胞迁移的关键调节因子，并且是后肢肌肉和前肢伸肌前体细胞靶向迁移所必需的。Lbx 1的异位表达诱导肌细胞标志物的表达，表明Lbx 1可能在控制肌肉前体细胞的迁移行为和决定其命运方面具有双重作用。此外，我们还揭示了shh在维持轴下肌细胞和形成由迁移前体细胞衍生的特定肌群中的作用。在下一阶段，我们将研究Lbx 1如何指定肢体肌肉前体细胞亚群的迁移路径。特别是，我们将使用敲入的LacZ基因分离杂合和纯合的Lbx 1表达细胞，并鉴定Lbx 1的推定靶基因。将在来自杂合和纯合小鼠的体节异种移植到鸡宿主胚胎中时分析细胞自主信息对靶细胞迁移的贡献。此外，我们将继续我们的努力，以表征的作用，分泌和膜结合分子直接迁移的肢芽前体细胞。我们还将产生双纯合子Lbx 1/Mox 2和Lbx 1/Pitx 1突变小鼠，以分析代偿调节途径和细胞向前肢和后肢迁移的差异。