PDF(Pubmed)
Abstract：
Synaptic development requires multiple signaling pathways to ensure successful connections. Transmembrane receptors are optimally positioned to connect the synapse and the rest of the neuron, often acting as synaptic organizers to synchronize downstream events. One such organizer, the LDL receptor-related protein LRP4, is a cell surface receptor that has been most well-studied postsynaptically at mammalian neuromuscular junctions. Recent work, however, identified emerging roles, but how LRP4 acts as a presynaptic organizer and the downstream mechanisms of LRP4 are not well understood. Here, we show that LRP4 functions presynaptically at Drosophila neuromuscular synapses, acting in motoneurons to instruct pre- and postsynaptic development. Loss of presynaptic LRP4 results in multiple defects, impairing active zone organization, synapse growth, physiological function, microtubule organization, synaptic ultrastructure and synapse maturation. We further demonstrate that LRP4 promotes most aspects of presynaptic development via a downstream SR-protein kinase, SRPK79D. These data demonstrate a function for presynaptic LRP4 as a peripheral synaptic organizer, highlight a downstream mechanism conserved with its CNS function in Drosophila, and underscore previously unappreciated but important developmental roles for LRP4 in cytoskeletal organization, synapse maturation and active zone organization.
摘要：
组织形态发生仍然知之甚少。在植物中,一个核心问题是发育器官的3D细胞结构如何有助于其最终形状。我们通过对胚珠形态发生的比较分析来解决这个问题，利用被子植物胚珠形状的多样性。这里,我们提供了以单细胞分辨率计算的卡米米娜hirsuta胚珠发育的3D数字地图集，并将其与拟南芥的等效地图集进行比较。我们引入了基于神经的拓扑分析，作为无偏检测细胞结构差异的工具，并通过比较形态计量学和视觉检查证实了两个同源组织之间的拓扑差异。我们发现拓扑结构的差异，细胞体积的变化和组织的生长模式在片状的整体和球形的chalaza，与胚珠曲率的差异有关。相比之下,辐射，尽管内部细胞拓扑结构和组织生长方式不同，但圆锥形胚珠原基和nucelli的形状相似。我们的结果支持这样的观点，即组织的结构组织与其在3D细胞结构的进化转变过程中对形状变化的敏感性有关。
