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

在上一个应用中，我们已经证明了同源框基因Lbx1以一种细胞自主的方式决定了肌肉前体细胞的迁移路线。我们的结果表明，Lbx1是肌肉前体细胞迁移的关键调节因子，也是前肢伸肌和后肢肌肉前体细胞定向迁移所必需的。Lbx1的异位表达诱导了肌肉细胞标志物的表达，提示Lbx1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在维持下轴肌细胞和形成由迁移前体细胞衍生的特定肌群中的作用。在接下来的一段时间里，我们将研究Lbx1如何指定肢体肌肉前体细胞亚群的迁移路径。特别是，我们将利用敲入的LacZ基因分离表达Lbx1的杂合子和纯合子细胞，并鉴定Lbx1的可能靶基因。在将杂合和纯合子小鼠的体节异种移植到鸡的宿主胚胎中，将分析细胞自主信息对靶向细胞迁移的贡献。此外，我们将继续努力确定分泌分子和膜结合分子在指导肢芽前体细胞迁移方面的作用。我们还将产生双纯合子Lbx1/Mox2和Lbx1/Pitx1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。

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.