On June 10th, Nature Cell Biology published online an article from ION entitled “Dishevelled promotes axon development by regulating atypical protein kinase C”. This study was conducted in the Laboratory of Synaptic Signaling, by graduate students and research assistants Xian Zhang, Ji Zhu, Guo-ying Yang, Qing-jie Wang and Lei Qian under the supervision of Dr. Zhen-Ge Luo.

   A mature neuron receives inputs from multiple dendrites and sends its output to other neurons via a single axon. This polarized morphology requires proper axonal/dendritic differentiation during development. The atypical protein kinase C (aPKC) in complex with PAR3 and PAR6 is required for axonal-dendritic differentiation, but the upstream factors responsible for regulating its activity are largely unknown. Dr. Luo’s laboratory found that down-regulation of Dishevelled (Dvl), an immediate downstream effector of Wnt, abrogated axon differentiation, whereas Dvl over-expression resulted in multiple axon formation. Interestingly, Dvl was associated with aPKC and this interaction resulted in aPKC stabilization and activation. Furthermore, the multiple axon formation resulting from Dvl over-expression was attenuated by expressing a dominant-negative aPKC in these neurons and over-expression of aPKC prevented the loss of axon caused by Dvl down-regulation. Finally, Wnt5a, a noncanonical Wnt, activated aPKC and promoted axon differentiation. The Wnt5a effect on axon differentiation was attenuated by down-regulating Dvl or inhibiting aPKC. Thus, Dvl-aPKC interaction can promote axon differentiation mediated by the PAR3-PAR6-aPKC complex. In addition to elucidating the basic mechanisms of neuronal development, the results presented in this paper also provide insight for studies of neuronal regeneration following injury.

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