Additive neurogenesis supported by multiple stem cell populations mediates adult spinal cord development: A spatiotemporal statistical mapping analysis in a teleost model of indeterminate growth

Abstract

The knifefish Apteronotus leptorhynchus exhibits indeterminate growth throughout adulthood. This phenomenon extends to the spinal cord, presumably through the continuous addition of new neurons and glial cells. However, little is known about the developmental dynamics of cells added during adult growth. The present work characterizes the structural and functional development of the adult spinal cord in this model organism through a comprehensive quantitative analysis of the spatial and temporal dynamics of new cells at various developmental stages. This analysis, based on a novel statistical mapping approach, revealed within the adult spinal cord a wide distribution of both mitotically active and quiescent Sox2-expressing stem/progenitor cells (SPCs). While such cells are particularly concentrated within the ependymal layer near the central canal, the majority of them reside in the parenchyma, resembling the distribution of SPCs observed in the mammalian spinal cord. The active SPCs in the adult knifefish spinal cord give rise to transit amplifying progenitor cells that undergo a few additional mitotic divisions before developing into Hu C/D+ neurons and S100+ glial cells. There is no evidence of long-distance migration of the newborn cells. The persistence of cell proliferation and differentiation, combined with low levels of apoptosis, leads to a continuous addition of cells to the existing tissue. Newly generated neurons have functional and behavioral relevance, as indicated by the integration of axons of new electromotor neurons into the electric organ of these weakly electric fish. This results in a gradual increase in the amplitude of the electric organ discharge during adult development. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1269-1307, 2017.

Cellular composition and organization of the spinal cord central canal during metamorphosis of the frog Xenopus laevis

“…In concordance with teleost fish, cells lining the central canal have been related with proliferative capacities, in these species basal proliferation occurs during spinal cord development, however at difference with larvae, parenchymal cells in fish also proliferate (Sîrbulescu et al, ). Further to proliferation function, these cells contributing to additive neurogenesis contributing with spinal cord development in teleost fish (Sîrbulescu et al, ). In addition, cells noncontacting the central canal present in the lateral domain were positive for BLBP and GS, revealing a glial nature of these cells in froglets.…”

Stem‐Cell‐Driven Growth and Regrowth of the Adult Spinal Cord in Teleost Fish

“…Individuals of A. leptorhynchus continue to grow after reaching sexual maturity, in terms of both total length and body mass (Ilieş et al , ). This indeterminate growth follows a non‐asymptotic, attenuating trajectory and includes brain (Zupanc and Horschke, ) and spinal cord (Sîrbulescu et al , ). A major, although not sole, factor mediating this growth is the addition of newly generated cells to existing tissue (Zupanc et al , ; Sîrbulescu et al , ) (for details, see “Additive Neurogenesis,” below).…”

“…This indeterminate growth follows a non‐asymptotic, attenuating trajectory and includes brain (Zupanc and Horschke, ) and spinal cord (Sîrbulescu et al , ). A major, although not sole, factor mediating this growth is the addition of newly generated cells to existing tissue (Zupanc et al , ; Sîrbulescu et al , ) (for details, see “Additive Neurogenesis,” below). It has been hypothesized that the continued growth of the CNS during adulthood is driven by the growth in the periphery through generation of new muscle fibers and new receptor cells (Zupanc, ; ).…”

“…Although constitutively proliferating cells in the spinal cord of several species of teleost fish have been known for nearly two decades (Alunni et al , ; Takeda et al , ; Sîrbulescu et al , ), the identity and distribution of these presumptive adult SPCs, the fate of their progeny, and the relationship between the dynamics of various developmental processes at the cellular level, and of growth patterns at the tissue level, have remained largely elusive. Some light has been shed on these aspects by a recent comprehensive spatiotemporal analysis of immunohistochemically identified cells in the adult spinal cord of A. leptorhynchus (Sîrbulescu et al , ).…”

“…Individual markers and marker combinations are indicated by corresponding color coding: Sox2+ ( blue ), PCNA+ ( green ), BrdU+ ( red ), Sox2+/PCNA+ ( teal ), PCNA+/BrdU+ ( dark yellow ), Sox2+/BrdU+ ( purple ), and Sox2+/PCNA+/BrdU+ ( gray ). From: Sîrbulescu et al (). [Colour figure can be viewed at wileyonlinelibrary.com]…”