Instituto de Medicina Molecular e Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
PLoS One. 2013 Jun 28;8(6):e68021. doi: 10.1371/journal.pone.0068021. Print 2013.
Accurate regulation of Notch signalling is central for developmental processes in a variety of tissues, but its function in pectoral fin development in zebrafish is still unknown.
METHODOLOGY/PRINCIPAL FINDINGS: Here we show that core elements necessary for a functional Notch pathway are expressed in developing pectoral fins in or near prospective muscle territories. Blocking Notch signalling at different levels of the pathway consistently leads to the formation of thin, wavy, fragmented and mechanically weak muscles fibres and loss of stress fibres in endoskeletal disc cells in pectoral fins. Although the structural muscle genes encoding Desmin and Vinculin are normally transcribed in Notch-disrupted pectoral fins, their proteins levels are severely reduced, suggesting that weak mechanical forces produced by the muscle fibres are unable to stabilize/localize these proteins. Moreover, in Notch signalling disrupted pectoral fins there is a decrease in the number of Pax7-positive cells indicative of a defect in myogenesis.
CONCLUSIONS/SIGNIFICANCE: We propose that by controlling the differentiation of myogenic progenitor cells, Notch signalling might secure the formation of structurally stable muscle fibres in the zebrafish pectoral fin.
Notch 信号的精确调控对于各种组织的发育过程至关重要，但它在斑马鱼胸鳍发育中的功能尚不清楚。
方法/主要发现： 在这里，我们表明，在发育中的胸鳍中， Notch 通路所必需的核心元件在肌肉前体所在的位置或附近表达。在 Notch 通路的不同水平阻断 Notch 信号，会导致肌肉纤维形成薄、波浪状、碎片化和机械强度弱，并导致内骨骼盘状细胞中的应激纤维丢失。尽管编码结蛋白和微管蛋白的结构肌肉基因在 Notch 破坏的胸鳍中正常转录，但它们的蛋白质水平严重降低，这表明肌肉纤维产生的弱机械力无法稳定/定位这些蛋白质。此外，在 Notch 信号中断的胸鳍中， Pax7 阳性细胞的数量减少，表明肌发生存在缺陷。
结论/意义： 我们提出， Notch 信号通过控制成肌祖细胞的分化，可能确保了斑马鱼胸鳍中结构稳定的肌肉纤维的形成。
