INSERM UMR-S 1270, F-75005 Paris, France.
Institut du Fer à Moulin, INSERM, Sorbonne Univeristy, F-75005 Paris, France.
Cells. 2023 Jan 5;12(2):225. doi: 10.3390/cells12020225.
A morphogen is a signaling molecule that induces specific cellular responses depending on its local concentration. The concept of morphogenic gradients has been a central paradigm of developmental biology for decades. Sonic Hedgehog (Shh) is one of the most important morphogens that displays pleiotropic functions during embryonic development, ranging from neuronal patterning to axon guidance. It is commonly accepted that Shh is distributed in a gradient in several tissues from different origins during development; however, how these gradients are formed and maintained at the cellular and molecular levels is still the center of a great deal of research. In this review, we first explored all of the different sources of Shh during the development of the nervous system. Then, we detailed how these sources can distribute Shh in the surrounding tissues via a variety of mechanisms. Finally, we addressed how disrupting Shh distribution and gradients can induce severe neurodevelopmental disorders and cancers. Although the concept of gradient has been central in the field of neurodevelopment since the fifties, we also describe how contemporary leading-edge techniques, such as organoids, can revisit this classical model.
形态发生素是一种信号分子，根据其局部浓度诱导特定的细胞反应。形态发生梯度的概念几十年来一直是发育生物学的核心范例。Sonic Hedgehog（Shh）是最重要的形态发生素之一，在胚胎发育过程中具有多种功能，从神经元模式形成到轴突导向。人们普遍认为，Shh 在发育过程中来自不同来源的几种组织中呈梯度分布；然而，这些梯度如何在细胞和分子水平上形成和维持仍然是大量研究的中心。在这篇综述中，我们首先探讨了神经系统发育过程中 Shh 的所有不同来源。然后，我们详细介绍了这些来源如何通过多种机制在周围组织中分布 Shh。最后，我们讨论了 Shh 分布和梯度的破坏如何导致严重的神经发育障碍和癌症。尽管梯度的概念自五十年代以来一直是神经发育领域的核心，但我们也描述了诸如类器官等当代前沿技术如何重新审视这一经典模型。
