Neural stem/progenitor cells are activated during tail regeneration in the leopard gecko (Eublepharis macularius)

J Comp Neurol. 2018 Feb 1;526(2):285-309. doi: 10.1002/cne.24335. Epub 2017 Oct 20.

Abstract

As for many lizards, the leopard gecko (Eublepharis macularius) can self-detach its tail to avoid predation and then regenerate a replacement. The replacement tail includes a regenerated spinal cord with a simple morphology: an ependymal layer surrounded by nerve tracts. We hypothesized that cells within the ependymal layer of the original spinal cord include populations of neural stem/progenitor cells (NSPCs) that contribute to the regenerated spinal cord. Prior to tail loss, we performed a bromodeoxyuridine pulse-chase experiment and found that a subset of ependymal layer cells (ELCs) were label-retaining after a 140-day chase period. Next, we conducted a detailed spatiotemporal characterization of these cells before, during, and after tail regeneration. Our findings show that SOX2, a hallmark protein of NSPCs, is constitutively expressed by virtually all ELCs before, during, and after regeneration. We also found that during regeneration, ELCs express an expanded panel of NSPC and lineage-restricted progenitor cell markers, including MSI-1, SOX9, and TUJ1. Using electron microscopy, we determined that multiciliated, uniciliated, and biciliated cells are present, although the latter was only observed in regenerated spinal cords. Our results demonstrate that cells within the ependymal layer of the original, regenerating and fully regenerate spinal cord represent a heterogeneous population. These include radial glia comparable to Type E and Type B cells, and a neuronal-like population of cerebrospinal fluid-contacting cells. We propose that spinal cord regeneration in geckos represents a truncation of the restorative trajectory observed in some urodeles and teleosts, resulting in the formation of a structurally distinct replacement.

Keywords: RRID 476811; RRID AB_10013382; RRID AB_10807945; RRID AB_11212768; RRID AB_1270870; RRID AB_1549592; RRID AB_2160375; RRID AB_221448; RRID AB_2576205; RRID AB_528506; RRID AB_823640; RRID AB_92184; cerebrospinal fluid contacting cell; ependymal layer; lizard; neurogenesis; radial glia; regeneration; reptile; spinal cord.

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • ELAV Proteins / metabolism
  • Ependyma / cytology
  • Gene Expression Regulation / physiology*
  • Lizards
  • Microscopy, Electron, Transmission
  • Microtubule Proteins / metabolism
  • Nerve Regeneration / physiology
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / physiology*
  • Neural Stem Cells / ultrastructure
  • Regeneration / physiology*
  • SOXB1 Transcription Factors / metabolism
  • Spinal Cord / cytology*
  • Spinal Cord / physiology
  • Tail / metabolism*
  • Tail / physiology
  • Tail / ultrastructure
  • Time Factors

Substances

  • ELAV Proteins
  • Microtubule Proteins
  • Nerve Tissue Proteins
  • SOXB1 Transcription Factors
  • Bromodeoxyuridine