Trisnadi Nathanie, Stathopoulos Angelike
Division of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, MC 114-96, Pasadena, California 91125.
Division of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, MC 114-96, Pasadena, California 91125
G3 (Bethesda). 2014 Dec 23;5(2):301-13. doi: 10.1534/g3.114.015891.
Gastrulation of the embryo involves coordinate cell movements likely supported by multiple signaling pathways, adhesion molecules, and extracellular matrix components. Fibroblast growth factors (FGFs) have a major role in Drosophila melanogaster mesoderm migration; however, few other inputs are known and the mechanism supporting cell movement is unclear. To provide insight, we performed an ectopic expression screen to identify secreted or membrane-associated molecules that act to support mesoderm migration. Twenty-four UAS insertions were identified that cause lethality when expressed in either the mesoderm (Twi-Gal4) or the ectoderm (69B-Gal4). The list was narrowed to a subset of 10 genes that were shown to exhibit loss-of-function mutant phenotypes specifically affecting mesoderm migration. These include the FGF ligand Pyramus, α-integrins, E-cadherin, Cueball, EGFR, JAK/STAT signaling components, as well as the heparan sulfate proteoglycan (HSPG) Terribly reduced optic lobes (Trol). Trol encodes the ortholog of mammalian HSPG Perlecan, a demonstrated FGF signaling cofactor. Here, we examine the role of Trol in Drosophila mesoderm migration and compare and contrast its role with that of Syndecan (Sdc), another HSPG previously implicated in this process. Embryos mutant for Trol or Sdc were obtained and analyzed. Our data support the view that both HSPGs function to support FGF-dependent processes in the early embryo as they share phenotypes with FGF mutants: Trol in terms of effects on mesoderm migration and caudal visceral mesoderm (CVM) migration and Sdc in terms of dorsal mesoderm specification. The differential roles uncovered for these two HSPGs suggest that HSPG cofactor choice may modify FGF-signaling outputs.
胚胎原肠胚形成涉及协调的细胞运动，这可能由多种信号通路、黏附分子和细胞外基质成分共同支持。成纤维细胞生长因子（FGFs）在黑腹果蝇中胚层迁移中起主要作用；然而，已知的其他影响因素很少，支持细胞运动的机制尚不清楚。为了深入了解这一过程，我们进行了异位表达筛选，以鉴定有助于支持中胚层迁移的分泌型或膜相关分子。我们鉴定出24个UAS插入片段，当它们在中胚层（Twi-Gal4）或外胚层（69B-Gal4）中表达时会导致胚胎致死。该列表被缩小到10个基因的子集，这些基因被证明表现出功能丧失突变表型， specifically影响中胚层迁移。其中包括FGF配体Pyramus、α-整合素、E-钙黏蛋白、Cueball、表皮生长因子受体（EGFR）、JAK/STAT信号成分，以及硫酸乙酰肝素蛋白聚糖（HSPG）“视叶严重减少”（Trol）。Trol编码哺乳动物HSPG基底膜聚糖的直系同源物，后者是一种已证实的FGF信号辅助因子。在这里，我们研究了Trol在果蝇中胚层迁移中的作用，并将其与Syndecan（Sdc）的作用进行比较和对比，Sdc是另一种先前涉及此过程的HSPG。我们获得并分析了Trol或Sdc突变的胚胎。我们的数据支持这样一种观点，即这两种HSPG都在早期胚胎中发挥作用，以支持FGF依赖的过程，因为它们与FGF突变体具有共同的表型：Trol影响中胚层迁移和尾侧内脏中胚层（CVM）迁移，而Sdc影响背侧中胚层特化。这两种HSPG所揭示的不同作用表明，HSPG辅助因子的选择可能会改变FGF信号输出。
