Effects of Fragile Mental Retardation Protein on Cerebellar Neuron Development and Migration in Mouse Model / 中国医科大学学报

Objective To investigate the effects of fragile X mental retardation protein（FMRP）on the development and migration of cerebellar neurons in mouse model.Methods Plasmids containing FMRPmutant-EGFP or EGFP were established and transfected into the lateral ventricle of the embryo mouse.Fragile X syndrome（FXS）genotype of the mouse model was identified.Nissl staining and immunofluorescence staining were conducted to assess the changes in neuron development and migration.Results In the experimental group,Nissl staining showed that the deep cerebellar neuclei contracted and divided by white matter,and the non-polarized Purkinje cells retained in internal granular layer;while immunofluorescence staining showed that Tbr2-positive unipolar brush cells changed the migration pathway and accumulated in the ventricular zone.Conclusion Cerebellar neurons showed abnormal formation and migration with the absence of FMRP.

TBR2-immunopsitive unipolar brush cells are associated with ectopic zebrin II-immunoreactive Purkinje cell clusters in the cerebellum of scrambler mice / 대한해부학회지

Unipolar brush cells (UBCs) are excitatory interneurons with their somata located in the granular layer. Recently, T-brain factor 2 (Tbr2) was shown to be expressed in a subset of UBCs in mouse cerebellum. Scrambler mice exhibit severe cerebellum abnormalities, including the failure of embryonic Purkinje cell dispersal and a complete absence of foliation due to a mutation in the disabled-1 adaptor protein. Since most UBC markers are expressed postnatally, it has proven difficult to identify the relationship between developing Purkinje cell clusters and migrating UBCs. Because scrambler mice closely mimic normal embryonic day 18 cerebellum, we examined whether Tbr2-positive UBCs are associated with Purkinje cell cluster markers such as zebrin II, which is the most studied compartmentation marker in the cerebellum. We investigated the distribution of Tbr2-positive UBCs in this mutant by using anti-Tbr2 immunocytochemistry. The data revealed that Tbr2 immunoreactivity was exclusively present in the nucleus of UBCs in scrambler cerebellum. Based on expression data, a Tbr2-positive UBC map was constructed. In addition, Tbr2-positive UBCs are found associated with ectopic zebrin II-immunoreactive Purkinje cell clusters in scrambler cerebellum. These data suggest that UBCs use Purkinje cell compartmentation to migrate into their final position through interactions with the embryonic array of specific Purkinje cell subtypes.

Distribution of Calretinin-immunoreactive Unipolar Brush Cells in Ataxic Mutant Pogo Mice Cerebellum / 대한해부학회지

Unipolar brush cells (UBCs) are a class of putative interneurons found in the granular layer of mammalian cerebellum and dorsal cochlear nucleus. The unipolar brush cells (UBCs), as with granular cells, which receives afferent synaptic input from extrinsic mossy fiber and whose axons branch in the granular layer and establish a system of cortex-intrinsic mossy fibers, which synapse with granule cells and other UBCs. In general, UBCs have been identified most readily by their expression of the calcium-binding protein, calretinin. The purpose of this study was to provide information about UBCs distributions of the new ataxic animal model, pogo mouse cerebellum using anti-calretinin immunohistochemistry, immunofluorescence and its effect on calcium homeostasis. Through the examination of calretinin immunohistochemistry and immunofluorescence, we observed that many calretinin immunoreactive UBCs were distributed widely throughout the lobules IX and X of the granular layer of both group. But, we found the number of calretinin immunoreactive UBCs of ataxic pogo (pogo/pogo) mouse was decreased and distribution pattern was altered, compared to control mouse. This result also suggest that reduced calretinin expression may effect on cerebellar Ca2+/-homeostasis, and it may in turn, explain the impaired motor coordination found in the ataxic pogo mice.