一般口演（Oral）

Oral Axon/Dendrite Growth and Circuit Formation-2 一般口演軸索と樹状突起の伸長と回路形成-2

7月27日（土）9:45～10:00　第9会場（朱鷺メッセ　3F　306+307） 3O-09m2-1 T細胞による末梢神経再生促進機構 Hirofumi Hohjoh（北條寛典），Kimie Nakagawa（中川公恵），Hiroshi Hasegawa（長谷川潤）神戸薬科大学　衛生化学研究室 The peripheral nerves can regenerate following a complete transection. Schwann cells, which are the glial cells of peripheral nerves, play a critical role in the peripheral nerve regeneration. In the injured peripheral nerve tissue, schwann cells dedifferentiate and migrate into the injury site and facilitate peripheral nerve regeneration via secretion of neurotrophic factors. Recently, it was revealed that proper peripheral nerve regeneration requires collective migration of schwann cells guided by newly formed blood vessels. Previously we found that T cells invade into the injured nerve and associate with blood vessels. But it is unclear whether T cells regulate angiogenesis and axon regeneration. Therefore, we investigated the role of T cells in peripheral nerve regeneration. 8 to 10 week old male adult C57BL/6J mice were used for all experiments. Sciatic nerve was exposed under anesthesia and transected at the mid-thigh. The transected nerve was sutured. Sciatic nerves were collected at 7 days after the surgery and used for gene expression analysis or immunostaining. To inhibit T cell invasion, 1 mg/kg FTY720 was intraperitoneally administrated everyday after the surgery. To test the role of T cells in peripheral nerve regeneration, we treated mice with FTY720, which inhibits T cell invasion into inflammatory tissues and examined blood vessels and axon density by immunostaining. The density of blood vessels increased in the injured nerves compared with intact nerves, and FTY720 suppressed the increase of blood vessel density. Moreover, FTY720 decreased regenerating axon density in the injured nerve. These data suggest that T cells facilitate angiogenesis and peripheral nerve regeneration. Next, to investigate how T cells facilitate axon regeneration, we studied gene expression in FTY720 treated mice. We found that several genes associated with axon regeneration (Gdnf, Bdnf) and schwann cell dedifferentiation (Ngfr) were upregulated by the peripheral nerve injury. Among these genes, the upregulation of Gdnf and Ngfr was suppressed by FTY720. These data indicate that T cells facilitate Gdnf and Ngfr expression in schwann cells. This study present the possibility that T cell-blood vessel-schwann cell axis facilitate peripheral nerve regeneration.		7月27日（土）10:00～10:15　第9会場（朱鷺メッセ　3F　306+307） 3O-09m2-2 Identification of phospholipase A₂ enzymes required for LysoPtdGlc/GPR55-mediated nociceptive circuit development Adam Tsuda Guy（Guy Adam Tsuda）¹，Mariko Inoue（Inoue Mariko）¹，Kei Yamamoto（Yamamoto Kei）^2,3,4，Yoshio Hirabayashi（Hirabayashi Yoshio）¹，Makoto Murakami（Murakami Makoto）^2,5,6，Hiroyuki Kamiguchi（Kamiguchi Hiroyuki）¹ ¹RIKEN Center for Brain Science ²Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science ³Faculty of Bioscience and Bioindustry, Tokushima University ⁴PRIME, Japan Agency for Medical Research and Development ⁵AMED-CREST, Japan Agency for Medical Research and Development ⁶Laboratory of Environmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo Previously we have described a novel lysophospholipid, lyso-phosphatidylglucoside (LysoPtdGlc), which acts as a chemorepulsive axon guidance cue in developing spinal cord through its activation of neuronal GPR55 (Guy et al., Science, 2015). LysoPtdGlc is a hydrolytic derivative of the membrane phospholipid phosphatidylglucoside (PtdGlc), which is produced by radial glia. Secreted phospholipase A₂ (sPLA₂) is a conserved family of isozymes that specifically hydrolyse the sn-2 ester of membrane phospholipids to produce diffusible lysophospholipids in the extracellular space. We hypothesised that sPLA₂ enzymes hydrolyse PtdGlc to LysoPtdGlc as the initial step of LysoPtdGlc/GPR55-mediated axon guidance. To test this, we analysed the spinal cord projections of nociceptive afferents in E14 mice in which specific sPLA₂ isozymes, PLA2G5 and PLA2G10, have been genetically deleted. Labelling sensory axons with DiI or antibodies to TrkA, we found that knockout mice lacking PLA2G5 or PLA2G10 showed similar abnormalities in their afferent projections in the spinal cord: an enlargement of the white matter in the dorsal cord and aberrant extension of nociceptive collateral axons into the medial grey matter. PLA2G10 knockout mice showed a stronger phenotype than PLA2G5. We speculate that the axon projection errors are caused by the inability of spinal cord cells to hydrolyse PtdGlc into LysoPtdGlc. Although sPLA₂ isozymes are implicated in many disease states, we have identified a role for sPLA₂ in nervous system development. We are now developing biochemical approaches to specifically target the sPLA₂/LysoPtdGlc/GPR55 signalling mechanism.

7月27日（土）10:15～10:30　第9会場（朱鷺メッセ　3F　306+307） 3O-09m2-3 分節特異的な軸索誘導が多様化した運動司令を実現する Suguru Takagi（高木優）¹，Akinao NOSE（能瀬聡直）^1,2 ¹東京大院理物理 ²東京大院新領域創成科学複雑理工 Adaptive behavior of an animal is underpinned by the complex yet precise connectivity of its nervous system. The connectivity of a neuron within the network is established through precise neurite guidance and synapse formation mechanisms, which give rise to the unique topological morphology of the neuron. Although much work has revealed the molecular and cellular basis of stereotypic network formation, the role of axon guidance in dictating animal behavior remains largely unexplored. We use Drosophila larvae as a model to study the circuit basis of action selection. In a previous study (Takagi et al., Neuron, 2017), we identified a class of segmentally-repeated command-like interneurons, that we named Wave, which drive distinct escape behaviors in a segment-specific manner. Activation of anterior Wave neurons (a-Waves) elicits backward locomotion, whereas activation of a posterior Wave neurons (p-Waves) promotes forward locomotion. Wave neurons in different segments exhibit distinct axon topologies, which are closely correlated to their divergent functions in behavioral regulation. Namely, while a-Waves extend their axons anteriorly to connect with backward-inducing circuits, p-Waves extend their axons posteriorly, possibly to connect with forward-inducing circuits. Here, we study the molecular mechanisms underlying the formation of segment-specific Wave connectivity. Candidate gene approach revealed an essential role of DFz4 in segment-specific Wave axon guidance: when DFz4 was knocked-down in Wave neurons by RNAi, the posterior extension of the p-Wave axon was greatly compromised while leaving the a-Waves axon intact. We identified DWnt4 as a candidate ligand for DFz4 in this process. DWnt4 mRNA is known to be enriched in the posterior end of the nerve cord, implicating DWnt4 as an attractive cue for p-Waves axons. The DFz4 knock-down mutants also showed abnormalities in Wave-driven motor outputs that are consistent with the axonal defects: induction of forward but not backward locomotion was significantly decreased in a fictive preparation. These results suggest that segment-specific axon guidance determines the role of Wave neurons in behavioral regulation. The present study demonstrates a causal link between neuronal morphology and behavioral regulation, revealing a design principle of neuronal circuitry from its anatomy to function.		7月27日（土）10:30～10:45　第9会場（朱鷺メッセ　3F　306+307） 3O-09m2-4 Neurogenetic origins of mathematical ability Michael Artur Skeide（Skeide Michael Artur）¹，Katharina Wehrmann（Wehrmann Katharina）^1,2，Bent Mueller（Mueller Bent）³，Holger Kirsten（Kirsten Holger）^3,4，Angela Friederici（Friederici Angela）¹ ¹Max Planck Institute for Human Cognitive and Brain Sciences ²University of Bern ³Fraunhofer Institute for Cell Therapy and Immunology ⁴Leipzig Research Center for Civilization Diseases Abstract Mathematical ability is heritable [1] and related to several genes expressing proteins in the brain [2-5]. It is unknown, however, which intermediate neural phenotypes could explain how these genes relate to mathematical ability. In the present study, we examined genetic effects on cerebral cortical volume of 3-6-year-old children without mathematical training to predict mathematical ability in school at 7-9 years of age. We found that ROBO1, a gene known to regulate prenatal growth of cerebral cortical layers [6], was specifically associated with the volume of the right parietal cortex, a key region for visuospatial quantity representation [7,8]. Individual volume differences in this region predicted more than a fifth of variance in mathematical ability. Our findings indicate that a fundamental genetic component of the quantity processing system is rooted in the early development of the parietal cortex. References 1. Rimfeld, K., et al. (2018). The stability of educational achievement across school years is largely explained by genetic factors. Sci. Learn. 3, 16. 2. Docherty, S.J., et al. (2010). A genome-wide association study identifies multiple loci associated with mathematics ability and disability. Genes Brain Behav. 9, 234-247. 3. Mascheretti, S., et al. (2014). KIAA0319 and ROBO1: evidence on association with reading and pleiotropic effects on language and mathematics abilities in developmental dyslexia. J. Hum. Genet. 59, 189-197. 4. Baron-Cohen, S., et al. (2014). A genome wide association study of mathematical ability reveals an association at chromosome 3q29, a locus associated with autism and learning difficulties: A preliminary study. PloS ONE 9, e96374. 5. Chen, H., et al. (2017). A genome-wide association study identifies genetic variants associated with mathematics ability. Sci. Rep. 7, 40365. 6. Gonda, Y., et al. (2013). ROBO1 regulates the migration and laminar distribution of upper-layer pyramidal neurons of the cerebral cortex. Cereb. Cortex 23, 1495-1508. 7. Nieder, A. (2016). The neuronal code for number. Nat. Rev. Neurosci. 17, 366-382. 8. Butterworth, B., and Walsh, V. (2011). Neural basis of mathematical cognition. Curr. Biol. 21, R618-621.