Department of Molecular Biology, Building 6L, Umeå University, Umeå S-90187, Sweden.
Development. 2013 Aug;140(15):3156-66. doi: 10.1242/dev.094466. Epub 2013 Jul 3.
The Jelly belly (Jeb)/Anaplastic Lymphoma Kinase (Alk) signalling pathway regulates myoblast fusion in the circular visceral mesoderm (VM) of Drosophila embryos via specification of founder cells. However, only a limited number of target molecules for this pathway are described. We have investigated the role of the Lame Duck (Lmd) transcription factor in VM development in relationship to Jeb/Alk signal transduction. We show that Alk signalling negatively regulates Lmd activity post-transcriptionally through the MEK/MAPK (ERK) cascade resulting in a relocalisation of Lmd protein from the nucleus to cytoplasm. It has previously been shown that downregulation of Lmd protein is necessary for the correct specification of founder cells. In the visceral mesoderm of lmd mutant embryos, fusion-competent myoblasts seem to be converted to 'founder-like' cells that are still able to build a gut musculature even in the absence of fusion. The ability of Alk signalling to downregulate Lmd protein requires the N-terminal 140 amino acids, as a Lmd(141-866) mutant remains nuclear in the presence of active ALK and is able to drive robust expression of the Lmd downstream target Vrp1 in the developing VM. Our results suggest that Lmd is a target of Jeb/Alk signalling in the VM of Drosophila embryos.
果冻 belly（Jeb）/间变性淋巴瘤激酶（Alk）信号通路通过指定创始细胞来调节果蝇胚胎圆形内脏中胚层（VM）中的成肌细胞融合。然而，该途径的仅有少数靶分子被描述。我们研究了 Lame Duck（Lmd）转录因子在与 Jeb/Alk 信号转导有关的 VM 发育中的作用。我们表明，Alk 信号通过 MEK/MAPK（ERK）级联反应在转录后负调节 Lmd 活性，导致 Lmd 蛋白从核重新定位到细胞质。先前已经表明，Lmd 蛋白的下调对于正确指定创始细胞是必要的。在 lmd 突变体胚胎的内脏中胚层中，融合有活性的成肌细胞似乎被转化为“创始样”细胞，即使没有融合，这些细胞仍能够构建肠道肌肉组织。Alk 信号下调 Lmd 蛋白的能力需要 N 端的 140 个氨基酸，因为在存在活性 ALK 的情况下，Lmd（141-866）突变体仍然保持在核内，并且能够驱动 Lmd 下游靶标 Vrp1 在发育中的 VM 中强烈表达。我们的结果表明，Lmd 是果蝇胚胎 VM 中 Jeb/Alk 信号的靶标。
