XB-ART-45180
Neural Dev
April 26, 2012;
7
13.
Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells.
Abstract
In contrast to mammals, amphibians, such as adult urodeles (for example, newts) and anuran larvae (for example, Xenopus) can regenerate their spinal cord after injury. However, the cellular and molecular mechanisms involved in this process are still poorly understood. Here, we report that tail amputation results in a global increase of Sox2 levels and proliferation of Sox2(+) cells. Overexpression of a dominant negative form of Sox2 diminished proliferation of spinal cord resident cells affecting tail regeneration after amputation, suggesting that spinal cord regeneration is crucial for the whole process. After spinal cord transection, Sox2(+) cells are found in the ablation gap forming aggregates. Furthermore, Sox2 levels correlated with regenerative capabilities during metamorphosis, observing a decrease in Sox2 levels at non-regenerative stages. Sox2(+) cells contribute to the regeneration of spinal cord after tail amputation and transection. Sox2 levels decreases during metamorphosis concomitantly with the lost of regenerative capabilities. Our results lead to a working hypothesis in which spinal cord damage activates proliferation and/or migration of Sox2(+) cells, thus allowing regeneration of the spinal cord after tail amputation or reconstitution of the ependymal epithelium after spinal cord transection.
PubMed ID: 22537391
PMC ID: PMC3425087
Article link: Neural Dev
Species referenced: Xenopus laevis
Genes referenced: dnai1 dpt nes sox2 tbxt vim
Antibodies: Sox2 Ab3
Article Images: [+] show captions
References [+] :
Agathocleous,
A directional Wnt/beta-catenin-Sox2-proneural pathway regulates the transition from proliferation to differentiation in the Xenopus retina.
2009, Pubmed,
Xenbase
Agathocleous,
A directional Wnt/beta-catenin-Sox2-proneural pathway regulates the transition from proliferation to differentiation in the Xenopus retina.
2009,
Pubmed
,
Xenbase
Agius, Endodermal Nodal-related signals and mesoderm induction in Xenopus. 2000, Pubmed , Xenbase
Avilion, Multipotent cell lineages in early mouse development depend on SOX2 function. 2003, Pubmed
Beattie, Metamorphosis alters the response to spinal cord transection in Xenopus laevis frogs. 1991, Pubmed , Xenbase
Beck, Molecular pathways needed for regeneration of spinal cord and muscle in a vertebrate. 2003, Pubmed , Xenbase
Becker, L1.1 is involved in spinal cord regeneration in adult zebrafish. 2004, Pubmed
Benraiss, Neurogenesis during caudal spinal cord regeneration in adult newts. 1999, Pubmed
Berg, Efficient regeneration by activation of neurogenesis in homeostatically quiescent regions of the adult vertebrate brain. 2010, Pubmed
Bylund, Vertebrate neurogenesis is counteracted by Sox1-3 activity. 2003, Pubmed
Chen, Control of muscle regeneration in the Xenopus tadpole tail by Pax7. 2006, Pubmed , Xenbase
Chernoff, Urodele spinal cord regeneration and related processes. 2003, Pubmed
Contreras, Early requirement of Hyaluronan for tail regeneration in Xenopus tadpoles. 2009, Pubmed , Xenbase
Dervan, Reaction of spinal cord central canal cells to cord transection and their contribution to cord regeneration. 2003, Pubmed
Drummond-Barbosa, Stem cells, their niches and the systemic environment: an aging network. 2008, Pubmed
Egar, The role of ependyma in spinal cord regeneration in the urodele, Triturus. 1973, Pubmed
Favaro, Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. 2009, Pubmed
Ferretti, Changes in spinal cord regenerative ability through phylogenesis and development: lessons to be learnt. 2003, Pubmed
Ferri, Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain. 2004, Pubmed
Forehand, Anatomical and behavioral recovery from the effects of spinal cord transection: dependence on metamorphosis in anuran larvae. 1982, Pubmed
Gargioli, Cell lineage tracing during Xenopus tail regeneration. 2004, Pubmed , Xenbase
Graham, SOX2 functions to maintain neural progenitor identity. 2003, Pubmed
Grotmol, A segmental pattern of alkaline phosphatase activity within the notochord coincides with the initial formation of the vertebral bodies. 2005, Pubmed
Guo, Transcription factor Sox11b is involved in spinal cord regeneration in adult zebrafish. 2010, Pubmed
Horky, Fate of endogenous stem/progenitor cells following spinal cord injury. 2006, Pubmed
Ke, Early response of endogenous adult neural progenitor cells to acute spinal cord injury in mice. 2006, Pubmed
Kishi, Requirement of Sox2-mediated signaling for differentiation of early Xenopus neuroectoderm. 2000, Pubmed , Xenbase
Le, Analysis of congenital hypomyelinating Egr2Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination. 2005, Pubmed
Lin, Regeneration of neural crest derivatives in the Xenopus tadpole tail. 2007, Pubmed , Xenbase
McDonald, Early events of peripheral nerve regeneration. 2008, Pubmed
McHedlishvili, A clonal analysis of neural progenitors during axolotl spinal cord regeneration reveals evidence for both spatially restricted and multipotent progenitors. 2007, Pubmed
Meletis, Spinal cord injury reveals multilineage differentiation of ependymal cells. 2008, Pubmed
Michel, Axonal-ependymal associations during early regeneration of the transected spinal cord in Xenopus laevis tadpoles. 1981, Pubmed , Xenbase
Mondia, Long-distance signals are required for morphogenesis of the regenerating Xenopus tadpole tail, as shown by femtosecond-laser ablation. 2011, Pubmed , Xenbase
Moreno, Biglycan is a new extracellular component of the Chordin-BMP4 signaling pathway. 2005, Pubmed , Xenbase
Mothe, Analysis of green fluorescent protein expression in transgenic rats for tracking transplanted neural stem/progenitor cells. 2005, Pubmed
Nordlander, The role of ependyma in regeneration of the spinal cord in the urodele amphibian tail. 1978, Pubmed
Pan, I-SceI meganuclease-mediated transgenesis in Xenopus. 2005, Pubmed , Xenbase
Parrinello, EphB signaling directs peripheral nerve regeneration through Sox2-dependent Schwann cell sorting. 2010, Pubmed
Poss, Advances in understanding tissue regenerative capacity and mechanisms in animals. 2010, Pubmed
Reimer, Motor neuron regeneration in adult zebrafish. 2008, Pubmed
SIMS, Transection of the spinal cord in developing Xenopus laevis. 1962, Pubmed , Xenbase
Schlosser, Thyroid hormone promotes neurogenesis in the Xenopus spinal cord. 2002, Pubmed , Xenbase
Shihabuddin, Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. 2001, Pubmed
Slack, The Xenopus tadpole: a new model for regeneration research. 2008, Pubmed , Xenbase
Sugiura, Differential gene expression between the embryonic tail bud and regenerating larval tail in Xenopus laevis. 2004, Pubmed , Xenbase
Suh, In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus. 2008, Pubmed
Sîrbulescu, Structural and functional regeneration after spinal cord injury in the weakly electric teleost fish, Apteronotus leptorhynchus. 2009, Pubmed
Tanaka, Considering the evolution of regeneration in the central nervous system. 2009, Pubmed
Taniguchi, Spinal cord is required for proper regeneration of the tail in Xenopus tadpoles. 2008, Pubmed , Xenbase
Thuret, Therapeutic interventions after spinal cord injury. 2006, Pubmed
Tseng, Tail regeneration in Xenopus laevis as a model for understanding tissue repair. 2008, Pubmed , Xenbase
Walder, Up-regulation of neural stem cell markers suggests the occurrence of dedifferentiation in regenerating spinal cord. 2003, Pubmed
Yoshino, Successful reconstitution of the non-regenerating adult telencephalon by cell transplantation in Xenopus laevis. 2004, Pubmed , Xenbase
Zappone, Sox2 regulatory sequences direct expression of a (beta)-geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells. 2000, Pubmed
Zhang, Recruitment of postmitotic neurons into the regenerating spinal cord of urodeles. 2003, Pubmed
Zupanc, Generation, long-term persistence, and neuronal differentiation of cells with nuclear aberrations in the adult zebrafish brain. 2009, Pubmed
Agius, Endodermal Nodal-related signals and mesoderm induction in Xenopus. 2000, Pubmed , Xenbase
Avilion, Multipotent cell lineages in early mouse development depend on SOX2 function. 2003, Pubmed
Beattie, Metamorphosis alters the response to spinal cord transection in Xenopus laevis frogs. 1991, Pubmed , Xenbase
Beck, Molecular pathways needed for regeneration of spinal cord and muscle in a vertebrate. 2003, Pubmed , Xenbase
Becker, L1.1 is involved in spinal cord regeneration in adult zebrafish. 2004, Pubmed
Benraiss, Neurogenesis during caudal spinal cord regeneration in adult newts. 1999, Pubmed
Berg, Efficient regeneration by activation of neurogenesis in homeostatically quiescent regions of the adult vertebrate brain. 2010, Pubmed
Bylund, Vertebrate neurogenesis is counteracted by Sox1-3 activity. 2003, Pubmed
Chen, Control of muscle regeneration in the Xenopus tadpole tail by Pax7. 2006, Pubmed , Xenbase
Chernoff, Urodele spinal cord regeneration and related processes. 2003, Pubmed
Contreras, Early requirement of Hyaluronan for tail regeneration in Xenopus tadpoles. 2009, Pubmed , Xenbase
Dervan, Reaction of spinal cord central canal cells to cord transection and their contribution to cord regeneration. 2003, Pubmed
Drummond-Barbosa, Stem cells, their niches and the systemic environment: an aging network. 2008, Pubmed
Egar, The role of ependyma in spinal cord regeneration in the urodele, Triturus. 1973, Pubmed
Favaro, Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. 2009, Pubmed
Ferretti, Changes in spinal cord regenerative ability through phylogenesis and development: lessons to be learnt. 2003, Pubmed
Ferri, Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain. 2004, Pubmed
Forehand, Anatomical and behavioral recovery from the effects of spinal cord transection: dependence on metamorphosis in anuran larvae. 1982, Pubmed
Gargioli, Cell lineage tracing during Xenopus tail regeneration. 2004, Pubmed , Xenbase
Graham, SOX2 functions to maintain neural progenitor identity. 2003, Pubmed
Grotmol, A segmental pattern of alkaline phosphatase activity within the notochord coincides with the initial formation of the vertebral bodies. 2005, Pubmed
Guo, Transcription factor Sox11b is involved in spinal cord regeneration in adult zebrafish. 2010, Pubmed
Horky, Fate of endogenous stem/progenitor cells following spinal cord injury. 2006, Pubmed
Ke, Early response of endogenous adult neural progenitor cells to acute spinal cord injury in mice. 2006, Pubmed
Kishi, Requirement of Sox2-mediated signaling for differentiation of early Xenopus neuroectoderm. 2000, Pubmed , Xenbase
Le, Analysis of congenital hypomyelinating Egr2Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination. 2005, Pubmed
Lin, Regeneration of neural crest derivatives in the Xenopus tadpole tail. 2007, Pubmed , Xenbase
McDonald, Early events of peripheral nerve regeneration. 2008, Pubmed
McHedlishvili, A clonal analysis of neural progenitors during axolotl spinal cord regeneration reveals evidence for both spatially restricted and multipotent progenitors. 2007, Pubmed
Meletis, Spinal cord injury reveals multilineage differentiation of ependymal cells. 2008, Pubmed
Michel, Axonal-ependymal associations during early regeneration of the transected spinal cord in Xenopus laevis tadpoles. 1981, Pubmed , Xenbase
Mondia, Long-distance signals are required for morphogenesis of the regenerating Xenopus tadpole tail, as shown by femtosecond-laser ablation. 2011, Pubmed , Xenbase
Moreno, Biglycan is a new extracellular component of the Chordin-BMP4 signaling pathway. 2005, Pubmed , Xenbase
Mothe, Analysis of green fluorescent protein expression in transgenic rats for tracking transplanted neural stem/progenitor cells. 2005, Pubmed
Nordlander, The role of ependyma in regeneration of the spinal cord in the urodele amphibian tail. 1978, Pubmed
Pan, I-SceI meganuclease-mediated transgenesis in Xenopus. 2005, Pubmed , Xenbase
Parrinello, EphB signaling directs peripheral nerve regeneration through Sox2-dependent Schwann cell sorting. 2010, Pubmed
Poss, Advances in understanding tissue regenerative capacity and mechanisms in animals. 2010, Pubmed
Reimer, Motor neuron regeneration in adult zebrafish. 2008, Pubmed
SIMS, Transection of the spinal cord in developing Xenopus laevis. 1962, Pubmed , Xenbase
Schlosser, Thyroid hormone promotes neurogenesis in the Xenopus spinal cord. 2002, Pubmed , Xenbase
Shihabuddin, Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. 2001, Pubmed
Slack, The Xenopus tadpole: a new model for regeneration research. 2008, Pubmed , Xenbase
Sugiura, Differential gene expression between the embryonic tail bud and regenerating larval tail in Xenopus laevis. 2004, Pubmed , Xenbase
Suh, In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus. 2008, Pubmed
Sîrbulescu, Structural and functional regeneration after spinal cord injury in the weakly electric teleost fish, Apteronotus leptorhynchus. 2009, Pubmed
Tanaka, Considering the evolution of regeneration in the central nervous system. 2009, Pubmed
Taniguchi, Spinal cord is required for proper regeneration of the tail in Xenopus tadpoles. 2008, Pubmed , Xenbase
Thuret, Therapeutic interventions after spinal cord injury. 2006, Pubmed
Tseng, Tail regeneration in Xenopus laevis as a model for understanding tissue repair. 2008, Pubmed , Xenbase
Walder, Up-regulation of neural stem cell markers suggests the occurrence of dedifferentiation in regenerating spinal cord. 2003, Pubmed
Yoshino, Successful reconstitution of the non-regenerating adult telencephalon by cell transplantation in Xenopus laevis. 2004, Pubmed , Xenbase
Zappone, Sox2 regulatory sequences direct expression of a (beta)-geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells. 2000, Pubmed
Zhang, Recruitment of postmitotic neurons into the regenerating spinal cord of urodeles. 2003, Pubmed
Zupanc, Generation, long-term persistence, and neuronal differentiation of cells with nuclear aberrations in the adult zebrafish brain. 2009, Pubmed