CRMP2在大脑发育过程中的作用

The proliferation, differentiation of the neuronal progenitor cells and migration and maturation of neurons are crucial for the normal formation of cerebral cortex and its function in mammalians. However, the underlying molecular mechanisms that control these processes are still not well understood. We have made CRMP2 conditional knockout mice to study the potential role that CRMP2 played during brain development. The mutant mice with deletion of CRMP2 in the brain showed significant smaller size and decreased body weight in comparison to the wild type mice. In this application, we propose to study whether or not CRMP2 plays an important role in neuronal development in neocortex by using CRMP2 cKO mice. The techniches including brain frozen sectioning, immunostaning, in utero electroporation and different behavior tests will be used. Meanwhile, the CRMP2 delta/delta mice will also be made and investigated. The function for CRMP2 in development, especcially in brain development will be illustrated in vivo in this study and its potential association with nervous disorders will also be verified.

哺乳动物大脑皮层功能结构的形成取决于神经前体细胞增殖和分化，以及神经元迁移和成熟等一系列过程。然而，对于控制这一系列过程的分子机制，还有待于深入的研究。鉴于CRMP2的前期研究提示其在大脑发育过程中具有重要作用，我们构建了CRMP2基因条件敲除小鼠的模型，通过跟Nestin-Cre小鼠交配，获得了在神经前体细胞中特异敲除CRMP2的CRMP2flox/flox; Nestin-Cre小鼠。初步观察到突变体小鼠具有个体小，体重轻的表型。本申请旨在利用这个动物模型，通过大脑切片、免疫染色、颅内电转、行为学实验等来深入地研究CRMP2在动物发育过程，尤其是在大脑神经发育过程中所起的作用。同时，我们也将进一步观察全身敲除掉CRMP2以后小鼠的表型及其与不同神经疾病的相关性。本研究具有重要的基础理论和潜在的医学应用价值。

哺乳动物大脑皮层功能结构的形成取决于神经前体细胞增殖和分化，以及神经元迁移和成熟等一系列过程。然而，对于控制这一系列过程的分子机制，还有待于深入的研究。鉴于CRMP2的前期研究提示其在大脑发育过程中具有重要作用，我们构建了CRMP2基因条件敲除小鼠的模型，通过跟Nestin-Cre小鼠交配，获得了在神经前体细胞中特异敲除CRMP2的CRMP2flox/flox; Nestin-Cre小鼠。突变体小鼠具有个体小，体重轻的表型。利用这个动物模型，我们通过大脑切片、免疫染色、颅内电转、行为学实验等深入地研究了CRMP2在动物发育过程，尤其是在大脑神经发育过程中所起的作用。发现全身敲除掉CRMP2以后小鼠具有精神分裂症类似的表型。本研究具有重要的基础理论和潜在的医学应用价值。