The Relationship Between Glial Adamlo Gene Knockout And Abnormalities Of The Cerebellum

Adam10gene is widely expressed in the cerebellum, suggesting that it may play an important role in the development of cerebellum. Adam10gene knockout at early stage of embryogenesis in the central nervous system leads to prenatal death of knockout mice and prevents our further research on the function of adamlO gene in the development of cerebellum. Through the use of CRE-LOXP system, we selectively knockouted the glia cells (including radial glial cells) adam10gene in mice. Thus, the adamlO gene knockout mice could survive as long as three weeks, which permitted us to study the role of the adamlO gene in cerebellar development. The adam10gene conditional knockout mice (CKO mice) showed abnormalities from embryonic18.5(E18.5), mainly on the morphology defects of the cerebellar foliation and cortex architecture. Glial cells in CKO mice appeared abnormal from E18.5as indicated by the disorder of the cell bodies at the adjacent folia. With the development of cerebellum, the abnormal morphological differentiation of the Bergmann glial cells was obviously. Most of the Bergmann glial cells lost radial protrusions and could not attach to the pial surface. At the same time, the glial cells BLBP protein was down-regulated and the glial cell apoptosis was increased. The granule cells mainly showed abnormal distribution. After postnatal4days, the granule cells began to cluster lining the fused folia;21days after birth, a considerable part of granule cells could not migrate into IGL and these cells accumulated at the meningeal surface or adjacent fused folia. In addition, the proliferation of granule cell precursors was decreased and the granule cells apoptosis was increased. Purkinje cells also displayed abnormal development whereas these changes were secondary and non-cell autonomous. After birth, it did not cause abnormal development of cerebellum by ablating the adam10gene in glial cells or granule cells. In CKO mice, the Notch I protein levels were down-regulated However, adam10knockout did not affect β-catenin, N-cadherin or L1protein expression. The results suggest that the adam10gene is critical for the formation of cerebellar foliation and cortex architecture and pay an important role in the migration of granule cells. More experiments are needed to dissect the underlying mechanisms.