Abstract
Zebrafish can repair their injured brain and spinal cord after injury unlike adult mammalian central nervous system. Any injury to zebrafish spinal cord would lead to increased proliferation and neurogenesis. There are presences of proliferating progenitors from which both neuronal and glial loss can be reversed by appropriately generating new neurons and glia. We have demonstrated the presence of multiple progenitors, which are different types of proliferating populations like Sox2+ neural progenitor, A2B5+ astrocyte/ glial progenitor, NG2+ oligodendrocyte progenitor, radial glia and Schwann cell like progenitor. We analyzed the expression levels of two common markers of dedifferentiation like msx-b and vimentin during regeneration along with some of the pluripotency associated factors to explore the possible role of these two processes. Among the several key factors related to pluripotency, pou5f1 and sox2 are upregulated during regeneration and associated with activation of neural progenitor cells. Uncovering the molecular mechanism for endogenous regeneration of adult zebrafish spinal cord would give us more clues on important targets for future therapeutic approach in mammalian spinal cord repair and regeneration.
Highlights
Unlike fish and urodele amphibians which can regenerate their CNS in adult life, the adult mammalian central nervous system (CNS) shows rather limited capacity to regenerate after injury
The present study demonstrates the presence of proliferating cells in the spinal cord of adult zebrafish when inflicted with crush injury and that may function as neural progenitor cells
The expression of Sox2 is upregulated in injured spinal cord as shown by time course analysis of sox2 mRNA and the highest level of expression is observed in 3 dpi cord (Fig 1D)
Summary
Unlike fish and urodele amphibians which can regenerate their CNS in adult life, the adult mammalian central nervous system (CNS) shows rather limited capacity to regenerate after injury. In the adult zebrafish brain, it has already been reported that different neuronal subtypes can be generated from different parts of brain other than olfactory bulb (OB) or hippocampal granule interneurons [5,9] Further studies involving this model might throw light into the mechanism(s) of generating different neuronal subtypes in regenerating cord similar to other parts of CNS. The proliferating progenitors in adult zebrafish brain and retina had been shown to have retained stem cell like properties, similar to what has been observed in mammalian CNS [10,15]. Both neurons and glias can be derived from adult neural progenitor as reported in teleost hind brain [16]
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