Follistatin Preferentially Antagonizes Activin Rather Than BMP Signaling in Drosophila

Follistatin Preferentially Antagonizes Activin Rather Than BMP Signaling in Drosophila
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DOI:
10.1002/dvg.20486
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发表时间:
2009-04-01
期刊:
影响因子:
1.5
通讯作者:
Arora, Kavita
Arora, Kavita
中科院分区:
生物学4区
文献类型:
--
作者:
Pentek, Jozsef;Parker, Louise;Arora, Kavita

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转化生长因子-β (TGF-β) 超家族的配体在整个动物界的胚胎模式和发育中发挥着重要作用。因此,影响配体稳定性、移动性和受体相互作用的细胞外因素也对发育产生深远的影响。卵泡抑素 (Fst) 就是此类调节因子之一,在脊椎动物中充当 TGF-β 配体的激活素和骨形态发生蛋白 (BMP) 亚家族的抑制剂。果蝇卵泡抑素 (fs) 编码 Fst 同源物,在整个发育过程中广泛表达,但该蛋白的体内功能仍不清楚。我们发现 fs 的过度表达会影响预蛹到蛹的转变和形态发生,强调了变态过程中 TGF-β 信号传导的新要求。此外,fs 表达会破坏神经元形态发生的各个方面,模仿激活素配体、Dawdle (Daw) 和激活素-β 的突变表型。在针对内源性 BMP 信号传导的测定中,我们没有发现 fs 可以拮抗 BMP 活性的证据。我们得出结论,fs 主要作为激活素抑制剂而不是 BMP 配体发挥作用。创世纪 47:261-273, 2009。(C) 2009Wiley-Liss, Inc.
Ligands of the transforming growth factor-beta (TGF-beta) superfamily play important roles in embryonic patterning and development throughout the animal kingdom. Consequently, extracellular factors that affect ligand stability, mobility, and receptor interaction also have profound effects on development. One such regulator, Follistatin (Fst), functions as an inhibitor of both activin and bone morphogenetic protein (BMP) subfamilies of TGF-beta ligands in vertebrates. Drosophila follistatin (fs) encodes a Fst homolog that is broadly expressed throughout development, but the in vivo function of the protein remains unclear. We show that overexpression of fs affects prepupal to pupal transition and morphogenesis, highlighting a novel requirement for TGF-beta signaling in metamorphosis. In addition, fs expression disrupts various aspects of neuronal morphogenesis, mimicking mutant phenotypes of the activin ligands, Dawdle (Daw) and Activin-beta. In assays targeting endogenous BMP signaling, we find no evidence that fs can antagonize BMP activity. We conclude that fs functions primarily as an inhibitor of activin rather than BMP ligands. genesis 47:261-273, 2009. (C) 2009Wiley-Liss, Inc.