| 研究概要 |
Radial glia cells are crucial to construct the nervous system. These neural progenitors display radial morphology with long radial processes which serve as physical scaffold for the developing neural tube. How their radial morphology is maintained while neural tube thickens during development, and how the integrity of radial morphology relates to their function are the key questions I aim to address in this project. We initially identified a mouse mutant deficient in CXCL12/CXCR4 signalling which displayed disrupted radial scaffold particularly evident in failure of some radial processes to contact the basement membrane at places in developing spinal cord. Using this mouse model, we found that the defect in radial processes did not compromise the proliferation or survival of these neural progenitor cells, but rather caused cells from the peripheral to invade into the central nervous system. An investigation of the molecular mechanism of CXCL12/CXCR4 in radial glia cells showed that CXCL12/CXCR4 signalling leads to a small but significant increase of radial glia’s adhesiveness to basement membrane components. Furthermore, CXCL12 stimulation increases the level of active form of cell adhesive molecule integrin B1 in radial glia cells. From these results, we propose a model that CXCL12/CXCR4 signalling strengthens radial processes’ adhesion to the basement membrane at least in part via activation of integrin B1 containing cell adhesion complexes, thereby contribute to the maintenance of the integrity of radial scaffold during neural tube development.
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