Differential and overlapping functions of two closely related Drosophila FGF8-like growth factors in mesoderm development
Differential and overlapping functions of two closely related Drosophila FGF8-like growth factors in mesoderm development
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DOI：
10.1242/dev.035451
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发表时间：
2009-07-15
期刊：
影响因子：
4.6
通讯作者：
Mueller, H. -Arno J.
中科院分区：
文献类型：
--
作者：
Klingseisen, Anna;Clark, Ivan B. N.;Mueller, H. -Arno J.
Thisbe （Ths）和Pyramus （Pyr）是脊椎动物成纤维细胞生长因子（FGF） 8/17/18亚家族的两个密切相关的果蝇同源物，是FGF受体冷血（Htl）的配体。这两种配体都是中胚层发育所必需的，但它们的不同表达模式表明在发育过程中具有不同的功能。我们产生了单突变体，发现这种或pyr功能丧失突变是半致死的，与两种配体或htl的丧失相比，突变体表现出更弱的表型。因此，pyr和这个在胚胎发生和生存能力方面显示出部分冗余。然而，我们发现pyr和这个单突变体在原胚和中胚层分化中表现出缺陷。我们发现，在迁移的中胚层细胞中，pyr的局部表达是正常细胞突出和高水平的MAPK激活所必需的。结果支持Pyr在原胚形成过程中作为中胚层迁移的指导性线索的模型。与此功能一致的是，pyr的突变会影响成心细胞的正常节段数量。此外，Pyr对于确定甚至跳过阳性的中胚层前体至关重要，而Pyr和Ths对于确定体细胞肌肉的一个子集都是必需的。结果表明，两个FGF8同源物在中胚层形态发生和分化中具有独立和重叠的功能。我们提出Pyr和这个功能的整合是htl依赖的中胚层扩散和分化的稳健性所必需的，但Pyr的功能已经变得更加特异性，可能代表了共同祖先基因复制后功能分化的早期阶段。
Thisbe (Ths) and Pyramus (Pyr), two closely related Drosophila homologues of the vertebrate fibroblast growth factor (FGF) 8/17/18 subfamily, are ligands for the FGF receptor Heartless (Htl). Both ligands are required for mesoderm development, but their differential expression patterns suggest distinct functions during development. We generated single mutants and found that ths or pyr loss-of-function mutations are semi-lethal and mutants exhibit much weaker phenotypes as compared with loss of both ligands or htl. Thus, pyr and ths display partial redundancy in their requirement in embryogenesis and viability. Nevertheless, we find that pyr and ths single mutants display defects in gastrulation and mesoderm differentiation. We show that localised expression of pyr is required for normal cell protrusions and high levels of MAPK activation in migrating mesoderm cells. The results support the model that Pyr acts as an instructive cue for mesoderm migration during gastrulation. Consistent with this function, mutations in pyr affect the normal segmental number of cardioblasts. Furthermore, Pyr is essential for the specification of even-skipped-positive mesodermal precursors and Pyr and Ths are both required for the specification of a subset of somatic muscles. The results demonstrate both independent and overlapping functions of two FGF8 homologues in mesoderm morphogenesis and differentiation. We propose that the integration of Pyr and Ths function is required for robustness of Htl-dependent mesoderm spreading and differentiation, but that the functions of Pyr have become more specific, possibly representing an early stage of functional divergence after gene duplication of a common ancestor.