Spatio-temporal neural stem cell behavior leads to both perfect and imperfect structural brain regeneration in adult newts

Abstract

Adult newts can regenerate large parts of their brain from adult neural stem cells (NSCs), but how adult NSCs reorganize brain structures during regeneration remains unclear. In development, elaborate brain structures are produced under broadly coordinated regulations of embryonic NSCs in the neural tube, whereas brain regeneration entails exquisite control of the re-establishment of certain brain parts, suggesting that a yet-unknown mechanism directs NSCs upon partial brain excision. Here we report that upon excision of a quarter of the adult newt (Pleurodeles waltl) mesencephalon, active participation of local NSCs around specific brain subregions’ boundaries leads to some imperfect and some perfect brain regeneration along an individual’s rostrocaudal axis. Regeneration phenotypes depend on how wound closing occurs using local NSCs, and perfect regeneration replicates development-like processes, but takes more than 1 year. Our findings indicate that newt brain regeneration is supported by modularity of boundary-domain NSCs with self-organizing ability in neighboring fields.