In contrast to mammals, salamanders and teleost fishes can efficiently repair the adult brain. It has been hypothesised that constitutively active neurogenic niches are a prerequisite for extensive neuronal regeneration capacity. Here, we show that the highly regenerative salamander, the red spotted newt, displays an unexpectedly similar distribution of active germinal niches with mammals under normal physiological conditions. Proliferation zones in the adult newt brain are restricted to the forebrain, whereas all other regions are essentially quiescent. However, ablation of midbrain dopamine neurons in newts induced ependymoglia cells in the normally quiescent midbrain to proliferate and to undertake full dopamine neuron regeneration. Using oligonucleotide microarrays, we have catalogued a set of differentially expressed genes in these activated ependymoglia cells. This strategy identified hedgehog signalling as a key component of adult dopamine neuron regeneration. These data show that brain regeneration can occur by activation of neurogenesis in quiescent brain regions.
This work was supported by grants from the Swedish Research Council, Karolinska Institute, Parkinsonfonden, Swedish Foundation for Strategic Research and Wenner-Gren Foundation to A.S., and by DFG TA274/4-1 in priority program Pluripotency, DFG TA274/2-2 Collaborative Research Center 655 from Cell to Tissues, and funds from the Max-Planck Institute and the Center for Regenerative Therapies to E.T. M.K. was supported by a long-term postdoctoral fellowship from HFSPO
Data Availability StatementSupplementary material
Supplementary material for this article is available at http://dev.biologists.org/lookup/suppl/doi:10.1242/dev.055541/-/DC1
- Adult neurogenesis
- Neuronal stem cell