발생중인 reeler 중뇌에서 도파민성 신경세포의 분포 이상
Malpositioning of mesencephalic dopaminergic neurons in developing reeler mice
- 주제(키워드) Reelin , dopaminergic neuron , midbrain , radial glial fiber , tangential nerve fiber
- 발행기관 아주대학교
- 지도교수 이영돈
- 발행년도 2010
- 학위수여년월 2010. 8
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000010939
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
The reelin, an extracellular glycoprotein plays important roles in neuronal migration and positioning during brain development. Reelin-deficient mice, reeler shows severe abnormalities in the lamination cerebral cortex. In addition to cerebral cortex and cerebellum, some brainstem nuclei defects have also been reported in reeler mice. Dopaminergic (DA) neurons are present in the diencephalon and in the mesencephalon that define specific subsets in terms of position and function. In the midbrain, there are three major cell groups: pars compacta of substantia nigra (SNc), the ventral tegmental area (VTA), and the retrorubral field (RRF). In reeler mice, DA neurons destined for the substantial nigra fail to migrate lateral has been documented. However, the distribution of DA cells as well as the cause of malposition in the other tyrosine hydroxylase (TH)-positive regions is not fully elucidated. Present study using TH immunohistochemistry shows that reeler mice exhibit neuronal malposition in substantia nigra par compacta (SNc, A9), ventral tegmental area (VTA, A10), and retrorubal field (RRF, A8). This abnormality was also found in Dab1-deficient, yotari mice. Brain lipid binding protein (BLBP) and RC2 labeling provide evidence that abnormal morphology of radial glial fibers is unable to guide DA neurons heading toward basal part of mesencephalon. Results from the Poly highly polysialylated neuronal cell adhesion molecule (PSA-NCAM) show that Reelin plays a role in the processes of tangential nerve fibers that guide the way to lateral part. These results suggest that reelin may function as a formation cue of processes in the radial glial and tangentially arranged fibers and the malformation affects the migration and position of mesencephalic DA neurons during development.
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CONTENTS
ABSTRACT Ⅰ
CONTENTS Ⅱ
LIST OF FIGURES Ⅳ
LIST OF ABBREVIATIONS Ⅴ
Ⅰ. INTRODUCTION
1. Reeler and Reelin signaling 1
2. Mesencephalic dopaminergic neurons 2
3. Migration of mesencephalic DA neurons 5
4. Purpose 7
Ⅱ. MATERIALS AND METHODS
A. ANIMALS 8
B. METHODS
1. Genotyping 8
2. Tissue preparation 9
3. Immunohistochemistry 10
4. Stereological analysis 10
Ⅲ. RESULTS
1. Malposition of midbrain DA neurons in reeler mice 12
2. Significant loss of SNc in reeler mice 14
3. Altered distribution of RRF in reeler mice 15
4. Malposition of midbrain DA neurons in yotari mice 16
5. The same number of DA neurons in the midbrain of wild type and reeler 18
6. A decrease of radial glial fibers in reeler 20
7. A lack of tangential nerve fibers in reeler mice and yotari mice 24
Ⅳ. DISCUSSION 26
Ⅴ. REFERENCE 30
국문요약 37
