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Reelin Is Necessary For Expression of Cell Adhesion Molecules during Radial Migration

Reelin이 신경세포 이동에 관여하는 세포접착분자의 발현에 미치는 영향

초록/요약

Radial glial cells in brain development serve as scaffolds which guide radial migration of cortical neurons. Recent studies show that many kinds of cell adhesion molecules (CAMs) are involved in glial-dependent mode of migration. Reelin plays a key role in neuronal migration and in the positioning of neurons within laminal structures during embryonic corticogenesis. It is also reported that activation of Reelin-Dab1 signaling facilitate the radial glial fiber maturation. In this study, we used neural stem cells (NSCs) culture technique and observed the effect of Reelin-Dab1 signaling on expression of CAMs between radial glial fibers and migrating neurons during radial migration. We observed that neuronal migration guided by RC2-positive radial glial fibers was significantly depressed in Reelin-Dab1 signaling lacking mice (reeler and yotari) than in wild type. During differentiation of NSC from reeler brain, expression level of N-cadherin and integrin α3β1 was lower than in wild type. However, when treated with Reelin to culture medium of wild type and reeler NSC, expression of CAMs was increased in both groups, suggesting that activation of Reelin-Dab1 signaling may facilitate expression of N-cadherin and integrin α3β1 interacting between radial glial fibers and migrating neurons during corticogenesis. In contrast, no difference in astrotactin expression level between wild type and reeler was observed. These results suggest a possibility that Reelin-Dab1 signaling may involve in the neuron-glia interaction for locomotion.

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목차

ABSTRACT i
TABLE OF CONTENTS ii
LIST OF FIGURES iv
LIST OF ABBREVIATION v
I. INTRODUCTION
1. Reelin signaling 1
2. Radial glia cells and radial migration 2
3. Differentiation of neural stem cells 3
4. Cell adhesion molecules 4
5. Purpose 6
II. MATERIALS AND METHODS
A. ANIMAL 7
B. METHODS
1. Genotyping 7
2. Culture of neurospheres 8
3. Immunofluorescence stain 9
4. Recombinant Reelin production 10
5. Table 1 - Antibodies used in this study 11

III. RESULTS
1. Formation of abnormal cortical layer and radial glia 12
2. Differentiation of radial glial cells in reeler 12
3. Reelin facilitates differentiation of neurospheres and radial glial fiber formation 15
4. Interaction between radial glial fibers and migrating neurons 19
5. Expression of CAMs between radial glial fibers and neurons 23
IV. DISCUSSION 28
V. REFERENCE 33
국문요약 43

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