Formosa-Jordan Pau, Ibañes Marta, Ares Saúl, Frade José-María
Department of Estructura i Constituents de la Matèria, Facultat de Física, Universitat de Barcelona, Barcelona, Spain.
Int J Dev Biol. 2013;57(5):341-50. doi: 10.1387/ijdb.120259jf.
Neuronal production in metazoans is tightly controlled by Delta/Notch-dependent signals regulating lateral inhibition. It is currently thought that lateral inhibition takes place in clusters of precursors with equal capacity to trigger and receive Notch-dependent inhibitory signals. However, this view neglects crucial dynamical aspects of the process. In this review, we discuss two of these dynamic factors, whose alterations yield dysfunctions in neurogenesis. First, precursors show variable neurogenic capacity as they go through the cell cycle. Second, differentiating precursors are in direct contact with non-neurogenic cells at the wavefront of expanding neurogenic domains. We discuss the mechanisms adopted by Metazoa to prevent these dysfunctions in the lateral inhibitory process, which include cell cycle synchronization occurring in the invertebrate neural epithelium and during primary neurogenesis in anamniotes, interkinetic nuclear movement in the vertebrate neuroepithelium and generalized Delta expression ahead of the neurogenic wavefront. The emerging concept is that lateral inhibition during neurogenesis occurs in dynamic clusters of precursors and requires specific mechanisms to avoid distortions resulting from the interaction between neurogenic and non-neurogenic precursors. The advance in visualizing Notch dynamics with real-time imaging at cellular and subcellular levels will notably contribute to our understanding of these novel "aspects of motion" in neurogenesis.
后生动物中的神经元生成由调节侧向抑制的Delta/Notch依赖性信号严格控制。目前认为，侧向抑制发生在前体细胞簇中，这些前体细胞触发和接收Notch依赖性抑制信号的能力相同。然而，这种观点忽略了该过程的关键动态方面。在这篇综述中，我们讨论了其中两个动态因素，它们的改变会导致神经发生功能障碍。首先，前体细胞在经历细胞周期时表现出可变的神经发生能力。其次，正在分化的前体细胞在不断扩大的神经发生区域的前沿与非神经发生细胞直接接触。我们讨论了后生动物为防止侧向抑制过程中出现这些功能障碍而采用的机制，其中包括无脊椎动物神经上皮和无羊膜动物初级神经发生过程中发生的细胞周期同步、脊椎动物神经上皮中的核间运动以及神经发生波前的普遍Delta表达。新出现的概念是，神经发生过程中的侧向抑制发生在前体细胞的动态簇中，并且需要特定机制来避免神经发生和非神经发生前体细胞之间相互作用导致的扭曲。在细胞和亚细胞水平上通过实时成像可视化Notch动态的进展将显著有助于我们理解神经发生中这些新的“运动方面”。
