본 연구에서는 소뇌의 발생과정에서 신경세포의 이동과 위치를 조절하는 reelin과 VLDLR 또는 ApoER2의 상관관계에 대해 조사하고자 하였다.래트와 마우스의 소뇌에서 VLDLR와 ApoER2의 발현을 살펴 본 결과 VLDLR의 발현이 ApoER2에 비해 높게 나타났다.래트에서는 VLDLR,ApoER2가 생후 7일에 발 현이 증가하였고 이후시기에 감소하였다.마우스에서 VLDLR는 생후 3일부터 발 현이 증가하여 생후 7일 이후에 감소하는 것으로 관찰되었고,ApoER2의 발현은 생후 14일에 증가하여 이후시기에 감소하였다.VLDLR는 소뇌에서 분자층과 조 롱박세포의 근위 가지돌기에서 주로 발현되고,ApoER2는 조롱박세포체에 국한 되어 발현되는 것을 관찰하였다. 또한 reelin이 결여된 reeler 마우스에서는 VLDLR의 발현이 정상 마우스에 비해 뚜렷이 증가한 것을 관찰하였으나 ApoER2는 정상과 차이를 보이지 않았다.이상의 결과를 통해 소뇌의 발생에 있 어 reelin 신호전달은 ApoER2보다는 VLDLR를 통해 주로 일어나며 이러한 VLDLR의 발현은 reelin에 의해 조절될 것으로 생각된다.
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- ABSTRACT -
Expression of Apolipoprotein E Receptor 2 (ApoER2) and Very Low Density Lipoprotein Receptor (VLDLR), Reelin Receptors in
Development of Cerebellar Cortex
Yu Mi Kim
Department of Medical Sciences The Graduate School, Ajou University
(Supervised by Professor Young Don Lee)
During brain development, reelin, an extracellular matrix protein regulates neuronal migration in the cerebral cortex, hippocampus, cerebellum and many other regions of mammalian brain. In the cortex, reelin is secreted by cajal-Retzius cells in the developing marginal zone and is required for inside-out layering of neurons in the cortical plate. Reelin binds to apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR) that are members of lipoprotein receptor family, and induces the tyrosine phosphorylation of disabled1 (Dab1), an adaptor protein binding to cytoplasmic domain of reelin receptors. Mice lacking reelin, Dab1, or both VLDLR and ApoER2, show identical phenotype and provide strong evidence for the involvement of these proteins in the same signaling axis.
In this study, we examined the correlation between the expression of reelin and VLDLR and ApoER2 during postnatal development of rat and mouse cerebellum. In developing rat and mouse cerebellum, the expression of VLDLR was prominent in developing molecular layer and proximal dendrites of Purkinje cells, whereas ApoER2 expression was mainly confined in Purkinje cells. In postnatal stages, the expression of both receptors was highest at postnatal day 7 and thereafter, significantly decreased. In reelin-deficient mice (reeler), ApoER2 level was not changed compared to wild type. However, VLDLR level in reeler was much higher than in wild type, showing that reelin may regulate the level of VLDLR rather than ApoER2 in cerebellar cortex formation. These results also suggested that VLDLR may primarily involve in the reelin-Dab1 signaling pathway in the postnatal development of cerebellar cortex.
Key Words: Reelin, VLDLR, ApoER2, Dab1, Cerebellar development, reeler