A salient feature of neurons is their intrinsic ability to grow and extend neurites, even in the absence of external cues. Compared to the later stages of neuronal development, such as neuronal polarization and dendri...A salient feature of neurons is their intrinsic ability to grow and extend neurites, even in the absence of external cues. Compared to the later stages of neuronal development, such as neuronal polarization and dendrite morphogenesis, the early steps of neuritogenesis remain relatively unexplored. Here we showed that redistribution of cortical actin into large aggregates preceded neuritoge- nesis and determined the site of neurite initiation. Enhancing actin polymerization by jasplakinolide treat- ment effectively blocked actin redistribution and neurite initiation, while treatment with the actin depolymerizing agents latrunculin A or cytochalasin D accelerated neurite formation. Together, these results demonstrate a critical role of actin dynamics and reorganization in neurite initi- ation. Further experiments showed that microtubule dynamics and protein synthesis are not required for neurite initiation, but are required for later neurite stabilization. The redistribution of actin during early neuronal develop- ment was also observed in the cerebral cortex and hip- pocampus in vivo.展开更多
基金the ION Optical Imaging Core Facility for technical supportthe IOBS-Nikon Biological Imaging Center for use of the N-SIM microscopesupported by grants from the National Natural Science Foundation of China(31125015 and31321091)
文摘A salient feature of neurons is their intrinsic ability to grow and extend neurites, even in the absence of external cues. Compared to the later stages of neuronal development, such as neuronal polarization and dendrite morphogenesis, the early steps of neuritogenesis remain relatively unexplored. Here we showed that redistribution of cortical actin into large aggregates preceded neuritoge- nesis and determined the site of neurite initiation. Enhancing actin polymerization by jasplakinolide treat- ment effectively blocked actin redistribution and neurite initiation, while treatment with the actin depolymerizing agents latrunculin A or cytochalasin D accelerated neurite formation. Together, these results demonstrate a critical role of actin dynamics and reorganization in neurite initi- ation. Further experiments showed that microtubule dynamics and protein synthesis are not required for neurite initiation, but are required for later neurite stabilization. The redistribution of actin during early neuronal develop- ment was also observed in the cerebral cortex and hip- pocampus in vivo.