シンポジウム（Symposium）

Symposium Molecular mechanisms for making species-specific neuronal circuits シンポジウム種特異的神経回路の構築と作動原理の解明協賛：新学術領域研究「脳構築における発生時計と場の連携」

7月27日（土）14:25～14:48　第5会場（朱鷺メッセ　3F　302） 3S05a-1 神経細胞の移動様式と哺乳類型大脳皮質構造の進化 Tadashi Nomura（野村真）京都府立医大神経発生生物学 The mammalian neocortex is a conspicuous brain structure characterized by a six-layered laminar organization with highly ordered neuronal circuits. During neocortical development, excitatory projection neurons migrate toward the brain surface by changing their shapes from multi-polar to bi-polar morphology, which accomplishes an inside-out pattern of cortical development. Deleterious changes in genetic and environmental factors significantly affect neuronal migration and consequence congenital cortical abnormalities. In contrast, a six-layered neocortex does not develop in non-mammalian species: all migratory neurons exhibit multi-polar shape and organize a three-layered dorsal cortex in reptiles, and nuclear structures in birds. However, molecular mechanisms underlying species-specific neuronal migration and cortical organization remain unclear. Here we identify that species-dependent regulations of Wnt signaling play an essential role in mammalian and reptilian corticogenesis. Temporal controls of Wnt signaling in migratory neurons are crucial for multipolar-to-bipolar conversion in mammals, and manipulation of Wnt signaling activity phenocopied species-specific neuronal morphologies in mammalian and reptilian cortex. Furthermore, we identified that reptilian and avian migrating neurons exhibit differential responses to altered Wnt activity. We suggest that heterochronic changes in Wnt activity contributed to the evolution of mammalian-type neuronal migration and an inside-out pattern of corticogenesis.		7月27日（土）14:48～15:11　第5会場（朱鷺メッセ　3F　302） 3S05a-2 ショウジョウバエの種特異的な求愛行動を生み出す神経メカニズム Ryoya Tanaka（田中良弥）¹，Tomohiro Higuchi（樋口智大）^2,3，Soh Kohatsu（古波津創）³，Kosei Sato（佐藤耕世）³，Takeshi Awasaki（粟崎健）⁴，Daisuke Yamamoto（山元大輔）³ ¹名古屋大学 ²東北大学 ³情報通信研究機構未来ICT研究所 ⁴杏林大学 Different animal species display different behavioral patterns, suggesting that the neural system can change to generate the behavioral diversification. However, the neural basis for the behavioral diversification among animal species remains largely unknown. To address this problem, we studied the neural circuitry for courtship behavior in Drosophila subobscura (D. subobscura), a species that displays unique courtship actions not shared by other members of the genus Drosophila, yet is phylogenetically related to D. melanogaster. It is known that the fruitless (fru) gene is a master regulator for the courtship circuitry formation in D. melanogaster, and therefore studies on the fru-labeled circuit in D. subobscura should allow us to reveal a difference in the circuitry for courtship behavior between the two species. We generated a D. subobscura fru variant strain, fru^soChrimV, by means of CRISPR-mediated transgenesis, which expresses the optogenetic activator protein Chrimson fused with the fluorescent marker Venus under the control of a native fru promoter. Stainings for Venus in fru^soChrimV heterozygotes revealed that this variant apparently recaptured the expression pattern of the fru gene; the fru-labeled circuitry in D. subobscura exhibits anatomical features similar to those of the D. melanogaster counterpart, including some sexually dimorphic structures. Optogenetic activation of the fru-labeled circuitry in fru^soChrimV heterozygotes induced some of mating behavior elements, including those specific to D. subobscura. These observations suggest that the fru-labeled circuitry controls the major part of courtship behavior in D. subobscura, including its subobscura-specific components.

7月27日（土）15:11～15:34　第5会場（朱鷺メッセ　3F　302） 3S05a-3 哺乳類大脳新皮質の発生・進化におけるサブプレートニューロンの役割 Chiaki Maruyama（丸山千秋）東京都医学総合研 The cerebral neocortex is responsible for higher order brain functions such as mental activity or speech in humans. In the human neocortex, billions of neurons are precisely arranged in an ordered 6-layered structure in inside-out fashion. This structure is formed by the sequential generation of neurons and their migration toward the brain surface called radial neuronal migration in the fetal period. Recently, we have reported that subplate neurons (SpNs) which are one of the earliest born and matured neuron in developing cerebral cortex, actively extend processes to form transient synapses on newly born multipolar migrating neurons and send signals to control their migration in mouse neocortex. This synaptic communication leads to switch from multipolar migration to locomotion. We observed the movements of newborn neurons of non-mammalian cortex by time-lapse imaging of cultured slices, and found that they don't switch the migration mode into locomotion. As SpNs are unique to mammals, they may have contributed to the evolution of mammalian neocortex by acquisition of locomotion mode which is a faster and efficient migration mode than multipolar migration. Besides this novel function in the radial migration, it has been well known that SpNs are the first cortical neurons to receive sensory input from thalamic axons. Then SpNs project axons toward layer IV neurons to establish a temporal link between thalamic axons and their final target in layer IV. After the completion of these important roles in corticogenesis, SpNs disappear in the postnatal stage. By increasing our knowledge about the functions of SpNs, we should be able to consider the SpNs as an organizer for mammalian neocortical formation by organizing multiple processes such as production of neurons, migration, axon pathfinding and synaptogenesis which progress simultaneously in the limited developmental period. In this presentation, I would like to discuss about the roles of SpNs in neocortical development and evolution with our recent data.		7月27日（土）15:34～15:57　第5会場（朱鷺メッセ　3F　302） 3S05a-4 Mechanisms regulating the formation of commissural projections in human, mouse and marsupial brain development Linda J Richards（Richards Linda J）^1,2，Rodrigo Suarez（Suarez Rodrigo）¹，Tobias Bluett（Bluett Tobias）¹，Annalisa Paolino（Paolino Annalisa）¹，Laura R Fenlon（Fenlon Laura R）¹，Laura Morcom（Morcom Laura）¹，Ilan Gobius（Gobius Ilan）¹，Peter Kozulin（Kozulin Peter）¹，Ryan Dean（Dean Ryan）¹，Timothy J Edwards（Edwards Timothy J）^1,3 ¹The University of Queensland, Queensland Brain Institute ²The University of Queensland, School of Biomedical Sciences ³The University of Queensland, Faculty of Medicine Long-range commissural connections are present in the nervous system of all bilaterally symmetrical animals. Their correct development depends on evolutionarily conserved principles that govern axonal pathfinding towards and across the midline. These include the presence of a suitable substrate including guidepost cells and the timed expression of receptors by the axons, and ligands expressed by the substrate or surrounding tissue. Another observation is the segregation of axons within major commissural tracts that correlate with their origin and projection to the contralateral hemisphere. To identify the crucial mechanistic drivers of commissure formation in mammals we are studying brain development in human, mouse and a marsupial species, Sminthopsis crassicaudata (commonly known as the fat-tailed dunnart). A significant difference between placental mammals and marsupials is that placental mammals evolved a third forebrain commissure called the corpus callosum. The expression of several transcription factors, such as Satb2, and the function of midline glial cells are crucial for the formation of the corpus callosum and we have identified similarities and differences in these mechanisms between placentals and marsupials. Recently, a highly conserved topography of cortical connections was identified in both species, indicating that this approach may yield mechanistic insights into the evolution of the corpus callosum. In addition to molecular mechanisms regulating commissure formation, the emergence of cortical activity may also play an important role in the development of correct commissural connections. A balance of inputs to both hemispheres is important for the final stages of callosal targeting in mice but the mechanisms underlying this phenomenon are still being investigated. Cross-species work using magnetic resonance imaging (MRI) enables investigations relevant for human commissure formation in animal models. Recent literature suggests that people with corpus callosum dysgenesis may have developed ectopic axonal tracts to compensate for the lack of a corpus callosum. Such tracts can be identified by diffusion MRI in humans and mice, and further investigations in mice are ongoing to determine their validity.

7月27日（土）15:57～16:20　第5会場（朱鷺メッセ　3F　302） 3S05a-5 CORTICAL LAYER WITH NO KNOWN FUNCTION Zoltan Molnar（Molnar Zoltan） University of Oxford Zoltan Molnar Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, South Parks Road, University of Oxford, Oxford, OX1 3QX, UK https://www.dpag.ox.ac.uk/team/zoltan-molnar http://orcid.org/0000-0002-6852-6004 The lowermost cell layer of the cerebral cortex that contains interstitial white matter cells in humans has great clinical relevance. These neurons express higher proportions of susceptibility genes linked to human cognitive disorders than any other cortical layer and their distribution is known to be altered in schizophrenia and autism (Hoerder-Suabedissen et al., 2013; Bakken et al., 2016). In spite of these clinical links, our current knowledge on the adult layer 6b is limited. These cells are the remnants of the subplate cells that are present in large numbers and play key role in the formation of cortical circuits but a large fraction of them die during postnatal development. The adult population that remains in all mammals to form interstitial white matter cells in human or layer 6b in mouse display unique conserved gene expression and connectivity (Hoerder-Suabedissen et al., 2018). We study their input and output using combined anatomical, genetic and physiological approaches. Selected cortical areas, relevant for sensory perception, arousal and sleep (V1, S1, M1, prefrontal cortex) are studied using chemogenetic and optogenetic methods. Our preliminary data suggest that 6b is not just a developmental remnant cell population in the adult, but a layer that plays a key role in cortical state control, integrating and modulating information processing (Guidi et al., 2016). Hoerder-Suabedissen et al., (2013) Proc Natl Acad Sci U S A. 110(9):3555-60. Bakken et al., (2016) Nature. 535(7612):367-75. Hoerder-Suabedissen et al., (2018) Cereb Cortex. 2018 28(5):1882-1897. Guidi et al., (2016) SFN Abstract 634.16. Supported by MRC (MR/N026039/1)