- Email: [email protected]
Roles of motoneruon-derived factor on sensory neuron development
Abstracts / Neuroscience Research 68S (2010) e55–e108
c-Fos expression (for approximately 12 hours) in solitary tract nucleus (a relay nuclei known to convey peripheral immune stimuli to broad brain regions) was normally observed. However, transient c-Fos expression (for approximately 6 hours) in hypothalamic paraventricular nucleus (PVN) was significantly attenuated, and that in central amygdala (for approximately 24 hours) was completely disappeared in KO mice. These results suggest that the central CRTH2 is selectively involved in the LPSinduced decrease in object exploration behavior, in which PVN and central amygdala might be involved. doi:10.1016/j.neures.2010.07.122
OY1-10-3-1 Phases of neuronal migration regulated by Rap1 in the developing cerebral cortex Katsutoshi Sekine 1 , Takeshi Kawauchi 1,2 , Ken-ichiro Kubo 1 , Takao Honda 1 , Kazunori Nakajima 1 1
Department of Anatomy, Keio University School of Medicine 2 PRESTO, JST, Saitama, Japan Mammalian cerebral cortex exhibits an organized laminar structure with 6 neuronal layers. During development, excitatory neurons generated around the lateral ventricule migrate radially in a long way towards the pial surface. Later-born neurons migrate past the earlier-born neurons to reach beneath the marginal zone, and cortical plate is formed in an inside-out manner. In the course of this migration, neurons change their shape and migratory behavior dynamically, and the final phase of radial migration is named as terminal translocation. Reelin is a glycoprotein secreted by the Cajal-Retzius cells in the marginal zone. The mutant mice of Reelin, Reelin receptors, and adaptor molecule Dab1 exhibit remarkable outside-in lamination in the cerebral cortex. This overall inversion of the laminar structure suggests that the Reelin-Dab1 signal is essential for the normal layer formation, but the function of Reelin-Dab1 signal for the inside-out lamination is not fully understood. Recently, it was shown that knock-down of Dab1 caused terminal translocation failure in a cell-autonomous manner. Our group have also established the mouse Dab1 knockdown vector independently, and confirmed that Dab1 is required for the terminal translocation. In order to clarify the molecular mechanisms of terminal translocation, we have focused on the function of Rap1 in this study.Rap1 is a small G protein that regulates cell proliferation, adhesion, and migration, and recent study showed that Reelin could activate C3G (Rap1 GEF) in vitro, and C3G mutant mice exhibited the failure of preplate splitting. We introduced dominant negative Rap1 or Rap1 GAP (inactivator of Rap1) by in utero electroporation and found phenotypes for radial migration. Based on the results, we will discuss the molecular basis of terminal translocation. doi:10.1016/j.neures.2010.07.123
OY1-10-3-2 LOTUS, a novel axon guidance molecule, functions as an endogenous Nogo antagonist Masumi Iketani , Yuji Kurihara, Yasufumi Sato, Yoshio Goshima, Kohtaro Takei Department of Molecular Pharmacology. and Neurobiology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan We discovered a novel axon guidance molecule LOTUS that serves for lateral olfactory tract (LOT) development of mouse telencephalon, and identified Nogo-66 receptor (NgR1) as its binding partner. Surprisingly, binding of NgR1 ligands such as Nogo-66 (Ng66) or myelin associated glycoprotein (MAG) to NgR1 was inhibited by LOTUS coexpressed with NgR1 in COS7 cells. We next examined if LOTUS exerts an antagonistic action on growth cone collapse induced by Ng66 in OB axons. Exogenously applied Ng66 did not induce growth cone collapse in cultured OB neurons in wild type of mice, while Ng66 induced growth cone collapse in lotus deficient mice. Furthermore, overexpression of LOTUS markedly attenuated the growth cone collapse induced by Ng66. These findings suggest that LOTUS exerts an antagonistic action on Ng66-induced repulsive signaling. doi:10.1016/j.neures.2010.07.124
e81
OY1-10-3-3 MKL, an actin-binding coactivator for SRF, is involved in activin-induced alteration of dendritic morphology and transcriptional activity in rat cortical neurons Mitsuru Ishikawa 1 , Naoki Nishijima 1 , Hiroyuki Sakagami 2 , Kunihiro Tsuchida 3 , Masaaki Tsuda 1 , Akiko Tabuchi 1 1
Biol. Chem., Med. & Pham. Sci., Toyama Univ 2 Dep. of Anatomy., Kitasato University, Sch of Med 3 Div. for Therapies against Intractable Diseases. Inst. for Comprehensive Med The function of the central nervous system is infinitely correlated with neuronal morphology both in development and adulthood. Accumulating studies have shown that MKL (MegaKaryoblastic Leukemia) family members, which are actin-binding proteins and also function as SRF (Serum Response Factor) coactivators, regulate neuronal morphology. In this study, we focus upon which extracellular ligands activate MKL-mediated morphological change in neurons. We demonstrate that activin, a member of transforming growth factor  (TGF-) superfamily, promotes SRF-mediated transcriptional activation and activin increases complexity of dendrites in rat cortical neurons, which are blocked by expression of MKL siRNA or inhibition of Rho signaling pathway. Furthermore activin-MKL signaling mediates the activation of -actin gene promoter. These results suggest that activin-MKL signaling is a novel pathway that regulates dendritic morphology of rat cortical neurons possibly through activating cytoskeletal gene expression. doi:10.1016/j.neures.2010.07.125
OY1-10-3-4 Roles of motoneruon-derived factor on sensory neuron development Noriyoshi Usui 1,2,3 , Keisuke Watanabe 3 , Katsuhiko Ono 4 , Nobuaki Tamamaki 4 , Kazuhiro Ikenaka 1,2 , Hirohide Takebayashi 3 1 Department of Physiological Science, School of Life Science, The Graduate University for Advanced studies (SOKENDAI), Hayama 2 Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki 3 Department of Morphological Neural Science, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 4 Department of Biology, Kyoto Prefectural University of Medicine, Kyoto
Execution of motor and sensory behaviors depends on circuitries integrating immediate sensory feedback to motor controlling activity. Motor and sensory circuitries are thought to interact during development, however, the molecular mechanisms are not fully understood. Here we show that roles of motoneuron (MN) on sensory neuron development. We found increased number of apoptotic cells in the dorsal root ganglia (DRG) of MNdeficient mice. Furthermore, abnormal axonal projections of sensory neurons were also observed both in the central nervous system (CNS) branch and the peripheral nervous system (PNS) branch. We focused on MN-derived neurotrophin-3 (NT-3), because NT-3 was primarily localized in MN strongly at early stages. NT-3-containing vesicle was observed in the axon of primary cultured MN. These data suggested that MN-derived NT-3 is one of the survival and axon guidance molecules for sensory neuron. doi:10.1016/j.neures.2010.07.126
OY1-10-4-1 Alteration of clock gene expression in the 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease Akane Hayashi , Naoya Matsunaga, Eriko Ikeda, Satoru Koyanagi, Shigehiro Ohdo Pharmaceutics, Faculty of Pharmaceutical Sci., Kyushu University, Fukuoka Purpose: Parkinson’s disease (PD) is a common neurodegenerative disorder that is characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN) and dopamine depletion in the striatum. Although the motor symptoms are still regarded as the main problem, non-motor symptoms in PD extremely also impair the quality of life. Several non-motor symptoms such as sleep disturbances and depression are suggested to be implicated in the alteration of circadian clock function. However, influence of PD on the expression of clock genes remains to be fully understood. In this study, we investigated the expression of clock genes and PD-related genes expression in Caudate-putamen (CPu) as well as the suprachiasmatic nucleus (SCN), a center of circadian clock, of MPTP-induced PD model mouse.
c-Fos expression (for approximately 12 hours) in solitary tract nucleus (a relay nuclei known to convey peripheral immune stimuli to broad brain regions) was normally observed. However, transient c-Fos expression (for approximately 6 hours) in hypothalamic paraventricular nucleus (PVN) was significantly attenuated, and that in central amygdala (for approximately 24 hours) was completely disappeared in KO mice. These results suggest that the central CRTH2 is selectively involved in the LPSinduced decrease in object exploration behavior, in which PVN and central amygdala might be involved. doi:10.1016/j.neures.2010.07.122
OY1-10-3-1 Phases of neuronal migration regulated by Rap1 in the developing cerebral cortex Katsutoshi Sekine 1 , Takeshi Kawauchi 1,2 , Ken-ichiro Kubo 1 , Takao Honda 1 , Kazunori Nakajima 1 1
Department of Anatomy, Keio University School of Medicine 2 PRESTO, JST, Saitama, Japan Mammalian cerebral cortex exhibits an organized laminar structure with 6 neuronal layers. During development, excitatory neurons generated around the lateral ventricule migrate radially in a long way towards the pial surface. Later-born neurons migrate past the earlier-born neurons to reach beneath the marginal zone, and cortical plate is formed in an inside-out manner. In the course of this migration, neurons change their shape and migratory behavior dynamically, and the final phase of radial migration is named as terminal translocation. Reelin is a glycoprotein secreted by the Cajal-Retzius cells in the marginal zone. The mutant mice of Reelin, Reelin receptors, and adaptor molecule Dab1 exhibit remarkable outside-in lamination in the cerebral cortex. This overall inversion of the laminar structure suggests that the Reelin-Dab1 signal is essential for the normal layer formation, but the function of Reelin-Dab1 signal for the inside-out lamination is not fully understood. Recently, it was shown that knock-down of Dab1 caused terminal translocation failure in a cell-autonomous manner. Our group have also established the mouse Dab1 knockdown vector independently, and confirmed that Dab1 is required for the terminal translocation. In order to clarify the molecular mechanisms of terminal translocation, we have focused on the function of Rap1 in this study.Rap1 is a small G protein that regulates cell proliferation, adhesion, and migration, and recent study showed that Reelin could activate C3G (Rap1 GEF) in vitro, and C3G mutant mice exhibited the failure of preplate splitting. We introduced dominant negative Rap1 or Rap1 GAP (inactivator of Rap1) by in utero electroporation and found phenotypes for radial migration. Based on the results, we will discuss the molecular basis of terminal translocation. doi:10.1016/j.neures.2010.07.123
OY1-10-3-2 LOTUS, a novel axon guidance molecule, functions as an endogenous Nogo antagonist Masumi Iketani , Yuji Kurihara, Yasufumi Sato, Yoshio Goshima, Kohtaro Takei Department of Molecular Pharmacology. and Neurobiology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan We discovered a novel axon guidance molecule LOTUS that serves for lateral olfactory tract (LOT) development of mouse telencephalon, and identified Nogo-66 receptor (NgR1) as its binding partner. Surprisingly, binding of NgR1 ligands such as Nogo-66 (Ng66) or myelin associated glycoprotein (MAG) to NgR1 was inhibited by LOTUS coexpressed with NgR1 in COS7 cells. We next examined if LOTUS exerts an antagonistic action on growth cone collapse induced by Ng66 in OB axons. Exogenously applied Ng66 did not induce growth cone collapse in cultured OB neurons in wild type of mice, while Ng66 induced growth cone collapse in lotus deficient mice. Furthermore, overexpression of LOTUS markedly attenuated the growth cone collapse induced by Ng66. These findings suggest that LOTUS exerts an antagonistic action on Ng66-induced repulsive signaling. doi:10.1016/j.neures.2010.07.124
e81
OY1-10-3-3 MKL, an actin-binding coactivator for SRF, is involved in activin-induced alteration of dendritic morphology and transcriptional activity in rat cortical neurons Mitsuru Ishikawa 1 , Naoki Nishijima 1 , Hiroyuki Sakagami 2 , Kunihiro Tsuchida 3 , Masaaki Tsuda 1 , Akiko Tabuchi 1 1
Biol. Chem., Med. & Pham. Sci., Toyama Univ 2 Dep. of Anatomy., Kitasato University, Sch of Med 3 Div. for Therapies against Intractable Diseases. Inst. for Comprehensive Med The function of the central nervous system is infinitely correlated with neuronal morphology both in development and adulthood. Accumulating studies have shown that MKL (MegaKaryoblastic Leukemia) family members, which are actin-binding proteins and also function as SRF (Serum Response Factor) coactivators, regulate neuronal morphology. In this study, we focus upon which extracellular ligands activate MKL-mediated morphological change in neurons. We demonstrate that activin, a member of transforming growth factor  (TGF-) superfamily, promotes SRF-mediated transcriptional activation and activin increases complexity of dendrites in rat cortical neurons, which are blocked by expression of MKL siRNA or inhibition of Rho signaling pathway. Furthermore activin-MKL signaling mediates the activation of -actin gene promoter. These results suggest that activin-MKL signaling is a novel pathway that regulates dendritic morphology of rat cortical neurons possibly through activating cytoskeletal gene expression. doi:10.1016/j.neures.2010.07.125
OY1-10-3-4 Roles of motoneruon-derived factor on sensory neuron development Noriyoshi Usui 1,2,3 , Keisuke Watanabe 3 , Katsuhiko Ono 4 , Nobuaki Tamamaki 4 , Kazuhiro Ikenaka 1,2 , Hirohide Takebayashi 3 1 Department of Physiological Science, School of Life Science, The Graduate University for Advanced studies (SOKENDAI), Hayama 2 Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki 3 Department of Morphological Neural Science, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 4 Department of Biology, Kyoto Prefectural University of Medicine, Kyoto
Execution of motor and sensory behaviors depends on circuitries integrating immediate sensory feedback to motor controlling activity. Motor and sensory circuitries are thought to interact during development, however, the molecular mechanisms are not fully understood. Here we show that roles of motoneuron (MN) on sensory neuron development. We found increased number of apoptotic cells in the dorsal root ganglia (DRG) of MNdeficient mice. Furthermore, abnormal axonal projections of sensory neurons were also observed both in the central nervous system (CNS) branch and the peripheral nervous system (PNS) branch. We focused on MN-derived neurotrophin-3 (NT-3), because NT-3 was primarily localized in MN strongly at early stages. NT-3-containing vesicle was observed in the axon of primary cultured MN. These data suggested that MN-derived NT-3 is one of the survival and axon guidance molecules for sensory neuron. doi:10.1016/j.neures.2010.07.126
OY1-10-4-1 Alteration of clock gene expression in the 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease Akane Hayashi , Naoya Matsunaga, Eriko Ikeda, Satoru Koyanagi, Shigehiro Ohdo Pharmaceutics, Faculty of Pharmaceutical Sci., Kyushu University, Fukuoka Purpose: Parkinson’s disease (PD) is a common neurodegenerative disorder that is characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN) and dopamine depletion in the striatum. Although the motor symptoms are still regarded as the main problem, non-motor symptoms in PD extremely also impair the quality of life. Several non-motor symptoms such as sleep disturbances and depression are suggested to be implicated in the alteration of circadian clock function. However, influence of PD on the expression of clock genes remains to be fully understood. In this study, we investigated the expression of clock genes and PD-related genes expression in Caudate-putamen (CPu) as well as the suprachiasmatic nucleus (SCN), a center of circadian clock, of MPTP-induced PD model mouse.