一般口演（Oral）

Oral Neurogenesis, Gliogenesis, Cellular Differentation-1 一般口演神経発生・グリア発生・細胞分化-1

7月25日（木）16:50～17:05　第8会場（朱鷺メッセ　3F　303+304） 1O-08e1-1 Mecom amplifies Notch output in phase with the cell cycle for neural stem cell self-renewal Adrian W Moore（Moore Adrian W）¹，Tobias Hohenauer（Hohenauer Tobias）¹，Elaine KY Chung（Chung Elaine KY）¹，Fatma Rabia Urun（Urun Fatma Rabia）^1,10，Hiroaki Taniguchi（Taniguchi Hiroaki）^1,2，Chee Wei Tee（Tee Chee Wei）^1,9，Saori Akimoto（Akimoto Saori）¹，Bogumil Kaczkowski（Kaczkowski Bogumil）³，Emi Kinameri（Kinameri Emi）¹，Mihoko Takahashi（Takahashi Mihoko）⁴，Rehab Abdelhamid（Abdelhamid Rehab）⁵，Ana Maria Suzuki（Suzuki Ana Maria）⁵，Susumu Goyama（Goyama Susumu）⁶，Mineo Kurokawa（Kurokawa Mineo）⁶，Erik Arner（Arner Erik）⁷，Takashi Umehara（Umehara Takashi）^4,11，Charles Plessy（Plessy Charles）⁸，Piero Carninci（Carninci Piero）⁵ ¹RIKEN Center for Brain Science ²Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, ³Laboratory for Genome Information Analysis, RIKEN Center for Integrative Medical Sciences ⁴Laboratory for Genome Information Analysis, RIKEN Center for Integrative Medical Sciences ⁵Laboratory for Transcriptome Technology, RIKEN Center for Integrative Medical Sciences ⁶Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo ⁷Laboratory for Applied Regulatory Genomics Network Analysis, RIKEN Center for Integrative Medical Sciences ⁸Genomics and Regulatory Systems Unit, Okinawa Institute of Science and Technology Graduate University ⁹School of Health Sciences, Universiti Sains Malaysia, Health Campus ¹⁰Graduate School of Science and Engineering, Saitama University ¹¹PRESTO, Japan Science and Technology Agency, Kawaguchi, Japan Building the nervous system requires external signaling pathways instruct neural stem cells to either self-renew or differentiate. The speed and amplitude of the transcriptional response determines signal outcome, as does cell cycle phase; here we demonstrate these critical parameters are linked through shared regulatory machinery. We find neural stem cell promoters for external signal response have a sharp architecture, that is associated with the chromatin regulator Wdr5. They include Hes1 that undergoes rapid pulses of induction downstream of Notch to drive self-renewal. The PRDM proto-oncogene Mecom recruits Wdr5 to the <I>Hes1</I> promoter, priming with PolII, and dramatically amplifying the pulse of Rbpj binding that induces transcription after Notch activation. Mecom levels rise during G1, focusing Hes1 amplification into this cell cycle stage. We propose molecular linkage of neural stem cell transcriptional-response dynamics to cell cycle phase illustrates a strategy for interpreting external signal action across different cancer and stem cell populations. EKYC was supported with a Japan Society for the Promotion of Science Postdoctoral Fellowship Program for Foreign Researchers, and Grants-in-Aid Young Scientists (B). TH was supported by a RIKEN Foreign Postdoctoral Researcher Fellowship. AWM and PC received funding for this study as part of the RIKEN ncRNA alliance. AWM was supported by a Japan Society for the Promotion of Science Grants-in-Aid Young Scientists (B) and Scientific Research (C).		7月25日（木）17:05～17:20　第8会場（朱鷺メッセ　3F　303+304） 1O-08e1-2 Ca²⁺依存性機構による細胞形態変化を介した大脳皮質放射状神経細胞移動の制御 Shin-ichiro Horigane（堀金慎一郎）^1,2,3，Sayaka Takemoto-Kimura（竹本―木村さやか）^1,2,3,4，Satoshi kamijo（上條諭志）³，Aki Adachi-Morishima（安達―森島亜希）³，Hajime Fujii（藤井哉）³，Haruhiko Bito（尾藤晴彦）³ ¹名古屋大学環境医学研究所神経系分野１ ²名古屋大学大学院医学系研究科分子神経科学 ³東京大学大学院医学系研究科神経生化学 ⁴JSTさきがけ During cortical circuit formation, spontaneous Ca²⁺ transients are observed in immature neurons even before sensory inputs stimulate neuronal firings, and preceding studies showed Ca²⁺ signaling regulates several aspects of neuronal development in the embryonic brain. Consistent with these findings, we previously reported that distinct limbs of the CaMKK-CaMKI cascade were specifically implicated in determining the extent of either dendritic or axonal growth. To further study the involvement of Ca²⁺ signaling in cortical circuit formation, we investigated whether Ca²⁺ signaling regulates radial migration of excitatory neurons in the embryonic cerebral cortex. To uncover the role of Ca²⁺ signaling in radial migration, we examined the intracellular Ca²⁺ dynamics of migrating neurons using GCaMP6s. We show that migrating neurons repeatedly display intracellular Ca²⁺ transients and Ca²⁺ events happen more frequently during slow-migrating and deceleration periods. Furthermore, we demonstrate that the forced Ca²⁺ elevation in migrating neurons changes migration rates that accompany morphological changes of these neurons. In order to elucidate the molecular mechanisms underlying these Ca²⁺ transients, we performed pharmacological studies, and found that the pharmacological induction of Ca²⁺ transients impairs radial migration. We are currently characterizing further downstream Ca²⁺-regulated events, especially phosphorylation, that ultimately control important aspects of radial migration. Taken together, our findings suggest that the Ca²⁺-dependent phosphorylation pathway governs cortical radial migration, and that dysregulation of Ca²⁺ signaling may lead to aberrant cortical circuit formation.

7月25日（木）17:20～17:35　第8会場（朱鷺メッセ　3F　303+304） 1O-08e1-3 成体嗅球の新生ニューロン移動における血流の役割 Takashi Ogino（荻野崇）¹，Masato Sawada（澤田雅人）¹，Hiroyuki Inada（稲田浩之）²，Naoko Kaneko（金子奈穂子）¹，Junichi Nabekura（鍋倉淳一）²，Kazunobu Sawamoto（澤本和延）^1,3 ¹名古屋市大医再生医学 ²生理学研究所発達生理学研究系生体恒常機能発達機構研究部門 ³生理学研究所神経発達・再生機構研究部門 In the adult mouse brain, neural stem cells still reside in the ventricular-subventricular zone and actively generate new neurons throughout life. These new neurons are continuously supplied to the adult olfactory bulb (OB), a primary processing center for odor information. After arriving at the OB, these new neurons migrate toward their final positions and differentiate into olfactory interneurons, granule cells and periglomerular cells, contributing to the odor processing. Previous reports suggest that blood vessels provide physical scaffold for neuronal migration in the rostral migratory stream and OB. However, the role of blood flow in neuronal migration remains unknown. Here, we performed in vivo two-photon imaging of migrating new neurons and blood flow in the adult OB, and analyzed their relationship in live animals. We found that adult-born neurons prefer to migrate and mature in the vicinity of blood vessels with high red blood cell (RBC) flow than those with low RBC flow. In addition, transmission electron microscopic analysis revealed that migrating new neurons are directly attached to the astrocytic endfeet that wrap vascular endothelial cells in the adult OB. To investigate the role of blood flow in neuronal migration, we locally manipulated blood flow in the adult OB, and found that migration of adult-born neurons is influenced by blood flow. Taken together, these results suggest that blood vessel-guided migration of adult-born neurons depends on blood flow in the OB.		7月25日（木）17:35～17:50　第8会場（朱鷺メッセ　3F　303+304） 1O-08e1-4 フォークヘッドボックス転写因子は強度依存性感覚処理回路のシナプス前特異性とシナプス伝達効率を決定する Sayaka Hori（堀沙耶香），Shohei Mitani（三谷昌平）東京女子医大院医生理学講座 Optimization of the types and timing of avoidance behaviors depending on the intensity of a noxious stimulus is essential for survival; however, processing in the central nervous system and its developmental bases are largely unknown. Here, we report that Caenorhabditis elegans preferentially selects one of three different types of avoidance behaviors depending on the strength of the noxious stimulus. We screened 279 neuronal transcription factors using a combination of optogenetics and RNA interference methods and identified 19 candidates required for avoidance behaviors. Two candidate genes, unc-130 (UNCoordinated 130), which encodes a human Forkhead box D4 (FOXD4) homolog, and fkh-9 (ForKHead transcription factor family 9), which encodes an human Forkhead box G1 (FOXG1) homolog, are required for the neural fate determination of the important interneurons for choice of avoidance behaviors, regulating the expression of a major chemical synapse gene, namely, an AMPA-type ionotropic glutamate receptor glr-1. However, both genes do not affect the expression of a component of invertebrate electrical synapses, namely gap junctions, inx-1 (innexin 1). In addition, the double mutants show dramatic accumulation of RAB-3, which normally localizes to the synaptic vesicles, in the neurites of AIB interneurons. Artificial excitation of AIB interneurons by Channelrhodopsin-2 cannot induce proper avoidance behaviors in the mutants. Both results imply that the reduction of neurotransmitter release is associated with the RAB-3 accumulation. Our study will provide a novel molecular basis of the unc-130/FOXD and fkh-9/FOXG1 to specify the synaptic functions for complex behavior.