Frohnhöfer Hans Georg, Geiger-Rudolph Silke, Pattky Martin, Meixner Martin, Huhn Carolin, Maischein Hans-Martin, Geisler Robert, Gehring Ines, Maderspacher Florian, Nüsslein-Volhard Christiane, Irion Uwe
Max-Planck-Institut für Entwicklungsbiologie, Abteilung 3, Spemannstrasse 35, Tübingen 72076, Germany.
Institut für Physikalische und Theoretische Chemie, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 18, Tübingen 72076, Germany.
Biol Open. 2016 Jun 15;5(6):736-44. doi: 10.1242/bio.018721.
Polyamines are small poly-cations essential for all cellular life. The main polyamines present in metazoans are putrescine, spermidine and spermine. Their exact functions are still largely unclear; however, they are involved in a wide variety of processes affecting cell growth, proliferation, apoptosis and aging. Here we identify idefix, a mutation in the zebrafish gene encoding the enzyme spermidine synthase, leading to a severe reduction in spermidine levels as shown by capillary electrophoresis-mass spectrometry. We show that spermidine, but not spermine, is essential for early development, organogenesis and colour pattern formation. Whereas in other vertebrates spermidine deficiency leads to very early embryonic lethality, maternally provided spermidine synthase in zebrafish is sufficient to rescue the early developmental defects. This allows us to uncouple them from events occurring later during colour patterning. Factors involved in the cellular interactions essential for colour patterning, likely targets for spermidine, are the gap junction components Cx41.8, Cx39.4, and Kir7.1, an inwardly rectifying potassium channel, all known to be regulated by polyamines. Thus, zebrafish provide a vertebrate model to study the in vivo effects of polyamines.
多胺是所有细胞生命所必需的小多阳离子。后生动物中存在的主要多胺是腐胺、亚精胺和精胺。它们的确切功能在很大程度上仍不清楚；然而，它们参与了影响细胞生长、增殖、凋亡和衰老的多种过程。在这里，我们鉴定了idefix，这是斑马鱼基因中编码亚精胺合酶的一个突变，通过毛细管电泳-质谱分析表明该突变导致亚精胺水平严重降低。我们发现亚精胺而非精胺对于早期发育、器官发生和色素模式形成至关重要。在其他脊椎动物中，亚精胺缺乏会导致非常早期的胚胎致死率，而斑马鱼中由母体提供的亚精胺合酶足以挽救早期发育缺陷。这使我们能够将它们与色素模式形成后期发生的事件区分开来。色素模式形成所必需的细胞相互作用中涉及的因素，可能是亚精胺的作用靶点，是缝隙连接成分Cx41.8、Cx39.4和内向整流钾通道Kir7.1，所有这些都已知受多胺调节。因此，斑马鱼提供了一个研究多胺体内作用的脊椎动物模型。
