The Wnt/Ca ²⁺ signaling pathway is essential for the regeneration of GABAergic neurons in planarian Dugesia japonica

The growth and differentiation of neurons are critical events in the establishment of proper neuron connectivity and function. Planarians have a remarkable ability to completely regenerate a functional nervous system from a pluripotent stem cell population. Thus, planarians provide a powerful model to identify genes required for neuronal differentiation in vivo. The Wnt/Ca²⁺ signaling pathway is crucial for cancer development, arousing inflammatory responses, and neurodegeneration. We analyzed the expression patterns and RNAi phenotypes for members of the Wnt/Ca²⁺ signaling pathway in the planarian, Dugesia japonica. The expression of DjWnt5a, DjPLC-β, DjCamKII, and DjCaln during regeneration was surprisingly similar and revealing in the regenerated brain. RNAi knockdown of DjWnt5a, DjPLC-β, DjCamKII, and DjCaln led to defects in regenerated brains including brain partial deletions, incompact phenotypes at the posterior of the new brain, and lateral branches, which could not regenerate. Furthermore, the expressions of GAD and the number of GABAergic neurons decreased. Together, these results suggest that the Wnt/Ca²⁺ signaling pathway is required for GABAergic neuron regeneration.

Keywords: GABAergic neuron; Wnt/Ca2+ signaling pathway; brain regeneration; function.