Fernandes-Silva Hugo, Correia-Pinto Jorge, Moura Rute Silva
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710‑057 Braga, Portugal.
ICVS/3B's-PT Government Associate Laboratory, 4710‑057 Braga/Guimarães, Portugal.
J Dev Biol. 2017 Mar 13;5(1):3. doi: 10.3390/jdb5010003.
The canonical hedgehog (HH) signaling pathway is of major importance during embryonic development. HH is a key regulatory morphogen of numerous cellular processes, namely, cell growth and survival, differentiation, migration, and tissue polarity. Overall, it is able to trigger tissue-specific responses that, ultimately, contribute to the formation of a fully functional organism. Of all three HH proteins, Sonic Hedgehog (SHH) plays an essential role during lung development. In fact, abnormal levels of this secreted protein lead to severe foregut defects and lung hypoplasia. Canonical SHH signal transduction relies on the presence of transmembrane receptors, such as Patched1 and Smoothened, accessory proteins, as Hedgehog-interacting protein 1, and intracellular effector proteins, like GLI transcription factors. Altogether, this complex signaling machinery contributes to conveying SHH response. Pulmonary morphogenesis is deeply dependent on SHH and on its molecular interactions with other signaling pathways. In this review, the role of SHH in early stages of lung development, specifically in lung specification, primary bud formation, and branching morphogenesis is thoroughly reviewed.
经典的刺猬信号通路（HH）在胚胎发育过程中至关重要。HH是众多细胞过程的关键调节形态发生素，即细胞生长与存活、分化、迁移和组织极性。总体而言，它能够引发组织特异性反应，最终有助于形成一个功能完备的生物体。在所有三种HH蛋白中，音猬因子（SHH）在肺发育过程中发挥着至关重要的作用。事实上，这种分泌蛋白水平异常会导致严重的前肠缺陷和肺发育不全。经典的SHH信号转导依赖于跨膜受体（如Patched1和Smoothened）、辅助蛋白（如刺猬相互作用蛋白1）以及细胞内效应蛋白（如GLI转录因子）的存在。总之，这种复杂的信号传导机制有助于传递SHH反应。肺形态发生在很大程度上依赖于SHH及其与其他信号通路的分子相互作用。在本综述中，将全面回顾SHH在肺发育早期阶段，特别是在肺特化、初级芽形成和分支形态发生中的作用。
