Zwarts Liesbeth, Goossens Tim, Clements Jason, Kang Yuan Y, Callaerts Patrick
Laboratory of Behavioral and Developmental Genetics, Department of Human Genetics, KU Leuven, LeuvenBelgium; Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie, LeuvenBelgium.
Department of Biology and Biochemistry, University of Houston, Houston, TX USA.
Front Cell Neurosci. 2016 Sep 5;10:210. doi: 10.3389/fncel.2016.00210. eCollection 2016.
Correct wiring of the mushroom body (MB) neuropil in the Drosophila brain involves appropriate positioning of different axonal lobes, as well as the sister branches that develop from individual axons. This positioning requires the integration of various guidance cues provided by different cell types, which help the axons find their final positions within the neuropil. Semaphorins are well-known for their conserved roles in neuronal development and axon guidance. We investigated the role of Sema-1a in MB development more closely. We show that Sema-1a is expressed in the MBs as well as surrounding structures, including the glial transient interhemispheric fibrous ring, throughout development. By loss- and gain-of-function experiments, we show that the MB axons display lobe and sister branch-specific Sema-1a signaling, which controls different aspects of axon outgrowth and guidance. Furthermore, we demonstrate that these effects are modulated by the integration of MB intrinsic and extrinsic Sema-1a signaling pathways involving PlexA and PlexB. Finally, we also show a role for neuronal- glial interaction in Sema-1a dependent β-lobe outgrowth.
果蝇大脑中蘑菇体（MB）神经纤维网的正确布线涉及不同轴突叶以及从单个轴突发育而来的姐妹分支的适当定位。这种定位需要整合不同细胞类型提供的各种导向线索，这些线索有助于轴突在神经纤维网中找到它们的最终位置。信号素因其在神经元发育和轴突导向中的保守作用而闻名。我们更深入地研究了信号素-1a在蘑菇体发育中的作用。我们发现，在整个发育过程中，信号素-1a在蘑菇体以及包括胶质瞬时半球间纤维环在内的周围结构中表达。通过功能丧失和功能获得实验，我们发现蘑菇体轴突表现出叶和姐妹分支特异性的信号素-1a信号传导，该信号传导控制轴突生长和导向的不同方面。此外，我们证明这些效应是由涉及PlexA和PlexB的蘑菇体内在和外在信号素-1a信号通路的整合来调节的。最后，我们还展示了神经-胶质相互作用在信号素-1a依赖的β叶生长中的作用。
