神経系の初期進化におけるニューレキシンの役割の研究

• Material Type: 博士論文
• Title: 神経系の初期進化におけるニューレキシンの役割の研究
• Author/Editor: Guzman, Christine
• Author Heading: Guzman, Christine
• Alternative Title: Investigating the Role of Neurexins in the Early Evolution of the Nervous System
• Pages: 1-
• Degree grantor/type: Okinawa Institute of Science and Technology Graduate University
• Date Granted: 2022-10-31
• Dissertation Number: 甲第106号
• Degree Type: Doctor of Philosophy
• Text Language Code: eng
• Target Audience: 一般
• Note (General): The appearance of the nervous system was an evolutionary event that allowed animals to control their physiology and behavior. In the nervous system, chemical signaling occurs either via volume transmission mainly by neuropeptides, or synaptic (wired) transmission by ‘classical’ chemical neurotransmitters. It is hypothesized that during the early evolution of animals, the diffusion-driven peptidergic signaling was the major mode of cell-cell communication, even for neuron-less animals. Later on, a faster and more targeted synaptic signaling was needed, as animal bodies and behaviors increased in complexity. But it remains largely unclear how the synaptic machinery evolved. One crucial event was the establishment of cell-cell contacts to specify and stabilize the communication between functionally distinct heterologous cell types like sensory neurons and muscles. In this study, I investigated Neurexins (Nrxns), a family of core presynaptic cell adhesion molecules with critical roles in bilaterian chemical synapse, using the non-bilaterian model Nematostella vectensis, a member of Cnidaria which is the closest outgroup to Bilateria. A series of gene expression and structure analyses indicated a non-neural origin of Nrxns. Functional analysis of the epithelial (classical) Nrxn in N. vectensis revealed its major role in cell adhesion, in particular in the maintenance of junction between ectodermal and endodermal epithelia. Neural Nrxns, named delta-Nrxns, are distinctly expressed in neuronal cell clusters that exhibit both peptidergic and classical neurotransmitter signaling abilities. Knockdown of NvNrxnδ1 and NvNrxnδ2 resulted in abnormal behaviors of N. vectensis polyps, involving muscle contraction. Interestingly, the knockdown of the neuropeptideprecursor gene co-expressed with delta-Nrxns did not show the same behavioral abnormalities, reflecting an independent role of delta-Nrxns from peptidergic signaling. Pharmacology experiments suggested that the delta-Nrxns are required for chemical neurotransmission (i.e., synaptic signaling). This study provides molecular, functional, and cellular insights into the ancestral non-neural function of Nrxns and may explain how and why this cell adhesion molecule family was employed in the synaptic machinery of the ancestral nervous system.
• DOI: 10.15102/1394.00002567
• Access Restrictions: インターネット公開
• Rights (production): © 2022 The Author
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 沖縄科学技術大学院大学 : OISTIR