Tectal stem cells display diverse regenerative capacities

Abstract

How diverse adult stem and progenitor populations regenerate tissue following damage to the CNS remains unknown across most neurogenic domains. To understand the role of quiescent radial-glial (qRG) stem cells during regeneration, we tested the hypothesis that qRG could be induced to proliferate and produce newborn neurons. We designed a stab lesion assay in the midbrain tectum of the adult zebrafish to target an isolated population of qRG, and investigated their proliferative behaviour, differentiation potential, and requirement of Wnt/{beta}-catenin signalling for the regenerative response. EdU-labelling showed that a small proportion of qRG transit to a proliferative state (pRG), but that progeny of pRG are restricted to a radial-glial fate. Lesion promoted upregulation of proliferation and neurogenesis from neuro-epithelial-like amplifying progenitors (NE-Ap) of the tectal marginal zone (TMZ). Homeostatic levels of Wnt/{beta}-catenin signalling persisted under lesioned conditions in the qRG/pRG population, whereby increased {beta}-catenin staining and axin2 expression was present in the NE-Ap progenitor zone. Attenuation of Wnt signalling using Dickkopf-1, demonstrated that proliferative responses post-injury appeared to be Wnt-independent. Our results align with the emerging view that adult stem/progenitor phenotypes are characterized by discrete, rather than mutual, regenerative programs and that different stem cell domains employ different modes of regeneration.