Oral Session

Oral Session 10 一般口演10

O10-1 How does Reelin signaling control the termination of neuronal migration? リーリンシグナルによるニューロン移動停止制御機構 Hirota Yuki（廣田ゆき），仲嶋一範 Dept. Anatomy, Keio Univ. School of Med. During neocortical development, neurons generated in the ventricular zone migrate towards the pial surface. In this process, later-born neurons pass through the existing layers consisting of earlier-born neurons and form superficial layers, resulting in a so-called “inside-out” pattern. This layer formation by neurons is regulated by several signaling cascades, including the Reelin signaling. Reelin is a glycoprotein mainly secreted by Cajal-Retzius neurons in the marginal zone (MZ), and known to function via its lipoprotein receptors, apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (Vldlr), and the cytoplasmic adaptor protein disabled 1 (Dab1). The Vldlr single mutant shows invasion of migrating neurons into the MZ without defect in the radial migration, whereas reeler mice lacking the Reelin protein, Apoer2/Vldlr double knockout mice and Dab1 mutants show severe migration defects with roughly inverted formation of the cortical layers, suggesting that Vldlr has specific roles for termination of neuronal migration beneath the MZ. However, precise mechanisms by which Reelin signaling controls the termination of neuronal migration remains unclear. Here, to gain insight into the role of Vldlr-mediated Reelin signaling during cortical development, we examined the migratory behavior of Vldlr-deficient neurons in the developing brain. Stage-specific labeling of newborn neurons revealed that the both the earlier-born and later-born neurons ectopically invaded the MZ in the Vldlr mutants. Rescue experiments showed that Vldlr has a cell-autonomous function and that adhesion molecules function downstream of Vldlr. These results suggest that Vldlr controls the proper termination of radial migration during cortical development.		O10-2 Reelin-Dab1 signaling controls detachment of chain-forming new neurons by regulating cell-cell adhesion Reelin-Dab1シグナルによる新生ニューロンの脱接着制御 Sawada Masato（澤田雅人）¹，藤掛数馬¹，金子奈穂子¹，Vicente Herranz-Perez²，本間夏美¹，柳川右千夫³，Jose Manuel Garcia-Verdugo²，服部光治⁴，澤本和延^1,5 ¹Dept Dev Regen Biol, Nagoya City Univ Grad Sch Med Sci, Nagoya, Japan ²Lab de Neurobiologia Comparada, Instituto Cavanilles, Universidad de Valencia, Spain ³Dept Genet Behav Neurosci, Gunma Univ Grad Sch Med, Maebashi, Japan ⁴Dept Biomed Sci, Grad Sch Pharma Sci, Nagoya City Univ, Nagoya, Japan ⁵Div Neural Dev Regen, NIPS, Okazaki, Japan Migrating neurons continuously change their cell-cell adhesion state by destroying and reconstructing adhesion structures in various aspects of brain development, such as exit from the neurogenic niche and the maintenance and termination of neuronal migration. The chain migration of new neurons in the postnatal brain is a powerful model for examining the dynamics of cell adhesion during neuronal migration. New neurons generated in the ventricular-subventricular zone form chain-like cell aggregates and migrate toward the olfactory bulb (OB) through the rostral migratory stream (RMS). After arriving at the OB, new neurons detach from the neuronal chains and start to migrate individually, eventually becoming integrated into the OB circuitry to contribute to olfactory functions. Previous reports suggest that Reelin induces detachment of new neurons from chains in the OB. However, the mechanism regulating cell-cell adhesion during the detachment process of chain migration remains unknown. Here we studied the function of Dab1, a downstream factor of Reelin, in the detachment of new neurons from chains in the postnatal OB. Reelin-mediated promotion of detachment of cultured new neurons from chains was canceled by Dab1 deficiency. The Dab1-deficient new neurons showed impaired migration from the RMS into the OB in cultured brain slices. Furthermore, Dab1 deficiency caused adherens junction-like structures to be sustained at the contact sites between new neurons during the detachment process. Together, our results suggest that the Reeling-Dab1 signaling-mediated regulation of cell-cell adhesion of new neurons is critical for their detachment from chains in the postnatal OB.

O10-3 Altered expression of GABAergic neuronal subtypes in prefrontal cortex by disruption of BRINP1 gene BRINP1の欠損による大脳皮質前頭前野のGABAニューロンサブタイプの発現変化 Kobayashi Miwako（小林三和子），林有一，藤本祐子，松岡一郎 Col. of Pharm. Sci., Matsuyama Univ., Matsuyama Japan BRINPs (BMP/RA-inducible Neural Specific Protein-1, 2, 3) are family genes expressed mainly in both the central and peripheral nervous system. BRINP1 is abundantly expressed in certain adult brain regions including cerebral cortex and hippocampus, with expression regulated in an activity-dependent manner in the dentate gyrus. Mice with disrupted BRINP1 gene exhibit abnormal behaviors such as increased locomotive activity and poor social activity which are analogous to symptoms of human psychiatric disorders such as schizophrenia (SCZ), autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).In the present study, to clarify the physiological roles of BRINP1 in psychiatric disorders, we examined the numbers of parvalbumin (PV)-expressing neurons and somatostatin (SST)-expressing neurons in the medial prefrontal cortex (mPFC) in BRINP1-KO mice. Immunohistochemical analysis revealed numbers of PV-expressing neurons and SST-expressing neurons in mPFC of BRINP1-KO mice were, respectively, 50% and 20% fewer than corresponding neurons in mPFC of wild-type mice. These data suggest that the abnormal behaviors related to human psychiatric disorders in BRINP1-KO mice could be derived from the hyperexcitability of pyramidal neurons as a consequence of decreased inhibitory innervation and conceivable dysregulation of the Excitatory/Inhibitory balance in mPFC.