Myat A, Henrique D, Ish-Horowicz D, Lewis J
Imperial Cancer Research Fund Developmental Biology Unit, Department of Zoology, University of Oxford, United Kingdom.
Dev Biol. 1996 Mar 15;174(2):233-47. doi: 10.1006/dbio.1996.0069.
In the Drosophila nervous system, lateral inhibition regulates commitment to a neural fate by preventing neighbouring cells from developing alike. This signalling process is mediated by two transmembrane proteins-Notch as receptor and Delta as its ligand. The Delta-related protein Serrate also acts as a Notch ligand in Drosophila, but in a different developmental process that organizes patterning of the wing. We have previously shown that lateral inhibition operates at early stages of neurogenesis in vertebrates, via genes homologous to Drosophila Delta and Notch. We report here the cloning of a chick Serrate homologue, C-Serrate-1. This gene is expressed in the central nervous system, as well as in the cranial placodes, nephric epithelium, vascular system, and distal limb-bud mesenchyme. In most of these sites, its expression is associated with expression of C-Notch-1 and C- Delta-1. All three genes are expressed in the ventricular zone of the hindbrain and spinal cord, throughout the period when neurons are being born. Within this zone, C-Delta-1 and C-Serrate-1 are expressed in complementary subsets of nondividing cells that appear to be nascent neurons: C- Serrate-1 expression is restricted to specific locations along the dorsoventral axis, forming narrow bands extending from the anterior hindbrain to the tail. Our observations strongly suggest that Delta-Notch signalling delivers lateral inhibition not only early but throughout vertebrate neurogenesis to regulate neuronal commitment, and that Serrate-Notch signalling may act similarly in this process. By analogy with its role in Drosophila wing patterning, C-Serrate-1 may also have a role in organising the dorso-ventral pattern of the neural tube. We argue that signalling via Notch maintains neurogenesis, both in vertebrates and in flies, by keeping a proportion of the neuroepithelial cells in an uncommitted stem-cell-like state.
在果蝇神经系统中，侧向抑制通过阻止相邻细胞发育成相同状态来调节神经命运的决定。这个信号传导过程由两种跨膜蛋白介导——作为受体的Notch和作为其配体的Delta。Delta相关蛋白锯齿蛋白（Serrate）在果蝇中也作为Notch配体起作用，但在一个不同的发育过程中，该过程负责翅膀的图案形成。我们之前已经表明，侧向抑制在脊椎动物神经发生的早期阶段起作用，通过与果蝇Delta和Notch同源的基因。我们在此报告鸡锯齿蛋白同源物C-Serrate-1的克隆。该基因在中枢神经系统以及颅基板、肾上皮、血管系统和远端肢芽间充质中表达。在这些部位中的大多数，其表达与C-Notch-1和C-Delta-1的表达相关。所有这三个基因在整个神经元生成期间都在后脑和脊髓的脑室区表达。在这个区域内，C-Delta-1和C-Serrate-1在似乎是新生神经元的非分裂细胞的互补亚群中表达：C-Serrate-1的表达局限于沿背腹轴的特定位置，形成从前脑后部延伸到尾部的窄带。我们的观察结果强烈表明，Delta-Notch信号传导不仅在早期而且在整个脊椎动物神经发生过程中传递侧向抑制以调节神经元命运的决定，并且锯齿蛋白-Notch信号传导在这个过程中可能也以类似方式起作用。与其在果蝇翅膀图案形成中的作用类似，C-Serrate-1可能在组织神经管的背腹图案方面也有作用。我们认为，通过Notch的信号传导在脊椎动物和果蝇中都维持神经发生，通过使一部分神经上皮细胞保持在未分化的干细胞样状态。
