On January 10th, Nature Neuroscience published an article from ION entitled “Semaphorin-3A guides radial migration of cortical neurons during development”. This study was conducted in the Laboratory of Neural Development, mainly by graduate students Gang Chen, Jian Sima, and Ming Jin under the supervision of Dr. Xiao-Bing Yuan.

The regulatory mechanism for neuronal migration in the developing cortex is a major unsolved problem in developmental neurobiology. It is generally accepted that the migration of newborn pyramidal neurons from the ventricular zone toward upper cortical layers is guided by radial glial fibers in the developing cortex, and that the laminar structure of the cortex is formed through regulated attachment and detachment of migrating neurons with radial glial fibers. However, whether the radial migration of cortical neurons can be guided by a gradient of diffusible factors is unknown, a potential guidance mechanism that has long been overlooked. The current study showed that the radial migration of cortical neurons during development is guided by the extracellular guidance molecule Semaphorin-3A, which is expressed in a descending gradient across cortical layers. By in utero electroporation, the authors were able to monitor the migration of a subpopulation of cortical neurons in their native environment and found that perturbing Semaphorin-3A signaling results in migration retardation with mis-orientation of affected neurons. Studies in cultured cortical slices with various perturbation showed that the endogenous gradient of Semaphorin-3A is required for the proper migration of newborn neurons. Transwell chemotaxis assays also showed that isolated newborn neurons were attracted by Semaphorin-3A. This is a first demonstration that radial migration of cortical neuron is guided by extracellular guidance factors. The inclusion of a chemotropism hypothesis in radial migration will help towards understanding how the highly ordered laminar structure of cortex is formed.

This work was supported by grants from CAS, National Natural Science Foundation of China, Shanghai Science and Technology Development Foundation, and “973” Programs.