Spatial Distribution of Prominin-1 (CD133) – Positive Cells within Germinative Zones of the Vertebrate Brain

József Jászai,Richard H W Funk,Elly M Tanaka,Michael Brand,Wieland B Huttner,Denis Corbeil,Sylvi Graupner,Debra L Silver

doi:10.1371/journal.pone.0063457

Abstract

BackgroundIn mammals, embryonic neural progenitors as well as adult neural stem cells can be prospectively isolated based on the cell surface expression of prominin-1 (CD133), a plasma membrane glycoprotein. In contrast, characterization of neural progenitors in non-mammalian vertebrates endowed with significant constitutive neurogenesis and inherent self-repair ability is hampered by the lack of suitable cell surface markers. Here, we have investigated whether prominin-1–orthologues of the major non-mammalian vertebrate model organisms show any degree of conservation as for their association with neurogenic geminative zones within the central nervous system (CNS) as they do in mammals or associated with activated neural progenitors during provoked neurogenesis in the regenerating CNS.MethodsWe have recently identified prominin-1 orthologues from zebrafish, axolotl and chicken. The spatial distribution of prominin-1–positive cells – in comparison to those of mice – was mapped in the intact brain in these organisms by non-radioactive in situ hybridization combined with detection of proliferating neural progenitors, marked either by proliferating cell nuclear antigen or 5-bromo-deoxyuridine. Furthermore, distribution of prominin-1 transcripts was investigated in the regenerating spinal cord of injured axolotl.ResultsRemarkably, a conserved association of prominin-1 with germinative zones of the CNS was uncovered as manifested in a significant co-localization with cell proliferation markers during normal constitutive neurogenesis in all species investigated. Moreover, an enhanced expression of prominin-1 became evident associated with provoked, compensatory neurogenesis during the epimorphic regeneration of the axolotl spinal cord. Interestingly, significant prominin-1–expressing cell populations were also detected at distinct extraventricular (parenchymal) locations in the CNS of all vertebrate species being suggestive of further, non-neurogenic neural function(s).Conclusion/InterpretationCollectively, our work provides the first data set describing a comparative analysis of prominin-1–positive progenitor cells across species establishing a framework for further functional characterization in the context of regeneration.

Highlights

Cellular and molecular characterization of neurogenic niches in the adult vertebrate nervous system is important in elucidating mechanisms underlying endogenous regenerative cascades as well as in elaborating potential cell-based therapeutic approaches
In the adult mammalian telencephalon, there are only two major foci described with constitutive neurogenic activity, which sharply contrasts the widespread embryonic neurogenesis observed along the entire neuraxis [1,2,3]
Taking advantage of the molecular information obtained within the mammalian brain [3.33,34], we have addressed whether characterization of the stem cell marker prominin-1 (CD133) could provide essential information, if not a signature, of germinative neurogenic zones of the non-mammalian vertebrate central nervous system (CNS)

Summary

Introduction

Cellular and molecular characterization of neurogenic niches in the adult vertebrate nervous system is important in elucidating mechanisms underlying endogenous regenerative cascades as well as in elaborating potential cell-based therapeutic approaches. In the adult mammalian telencephalon, there are only two major foci described with constitutive neurogenic activity, which sharply contrasts the widespread embryonic neurogenesis observed along the entire neuraxis [1,2,3]. The significance of this adult phenomenon is not fully understood, but recent findings indicate that it might have an impact among others on spatial memory [4,5]. Characterization of neural progenitors in non-mammalian vertebrates endowed with significant constitutive neurogenesis and inherent selfrepair ability is hampered by the lack of suitable cell surface markers. We have investigated whether prominin-1– orthologues of the major non-mammalian vertebrate model organisms show any degree of conservation as for their association with neurogenic geminative zones within the central nervous system (CNS) as they do in mammals or associated with activated neural progenitors during provoked neurogenesis in the regenerating CNS

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Results

Discussion

Conclusion