Expression of Apolipoprotein E Receptor 2 (ApoER2) and Very Low Density Lipoprotein Receptor (VLDLR), Reelin Receptors in Development of Cerebellar Cortex
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.
Reelin, VLDLR, ApoER2, Dab1, 소뇌발생, reeler, Cerebellar development
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