Regeneration of lost brain tissues by genetic manipulation of nou-darake in Schmidtea mediterranea planarians

Abstract

Neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s disease,affect up to 40 million people worldwide. These diseases in humans work by slowly degradingneural structures, but some species, such as planarians, can combat such afflictions by theirrobust regenerative properties. While it is known that the progressive loss of neural structures arecommon in these diseases, it is not known whether regeneration of neural structures can restorethe brain as it was. Our objective is to inhibit nou-darake (ndk), a gene associated withectopic brain formation, in genetically modified Schmidtea mediterranea planarians andanalyze both partial and full neural regeneration. Our general strategy starts by thedevelopment of three different planarian models utilizing RNA interference (RNAi): (1) SmedTOR(RNAi)planarians which exhibit only wound-healing abilities similar to humans, (2) Smedapc(RNAi)planarians which have disrupted anterior-posterior (A-P) polarity regenerating onlyposterior ends after amputation, and (3) Smed-βcatenin-B(RNAi) planarians which have disruptedA-P polarity regenerating only anterior ends after amputation. Afterwards, each planarian modelwill be given Smed-ndk(RNAi) and observed intact and after amputation. The proposed study willnot only present detailed spatiotemporal images of neural regeneration in multiple planarianmodels, but propose the planarian as a model organism for future neurodegenerative research. Our goal is to further the understanding of both partial and full neural regeneration in order tobring forth new treatments for neurodegenerative diseases.