Seminar: Juan Larrain

Cellular and molecular mechanism of spinal cord regeneration in the frog Xenopus laevis

Date:
6 March 2017 14:00 hrs. - 15:00 hrs.
Location:
Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289
Title:
Cellular and molecular mechanism of spinal cord regeneration in the frog Xenopus laevis
Speaker(s):

Juan Larrain, Pontificia Universidad Católica de Chile, Santiago, Chile

Host(s):

Gert-Jan Veenstra, Dept. of Developmental Molecular Biology, RIMLS

06-03-2017 14:00:0006-03-2017 15:00:00Europe/AmsterdamCellular and molecular mechanism of spinal cord regeneration in the frog Xenopus laevis Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289Rimlsrimls@radboudumc.nl

Remarks / more information:

Flyer

undefinedThe frog Xenopus laevis at larvae stages (stage 50-54, R-stages) regenerate in response to spinal cord injury (SCI) a capability that is lost at the metamorphic climax (stage 56-66, NR-stages), providing a unique model system to study spinal cord regeneration.

We carry out a detailed analysis of the cellular response to spinal cord injury using immunofluorescence, two-photon microscopy and transmission and scanning electron microscopy. In R-stage animals the spinal cord rapidly closes the central canal, the ventricular layer have very low levels of cell death and a massive proliferation of neural progenitor/radial glial cells expressing Sox2/3+ and new neurons are formed in the ablation gap. Knockdown of Sox2/3 impairs regeneration. A different response was observed in NR-stages with massive cell death, no proliferation and accumulation of glial cells rich in intermediate filaments and extracellular matrix components in the injury site. Using cell transplantation experiments we found that spinal cord cells isolated from R- stages and transplanted into NR-stage facilitate axon growth and axon regeneration, something that was not observed when donor cells come form NR-stages. All together these results demonstrate that R-animals, but not the NR, are enriched in neural progenitor/radial glial cells that in response to injury proliferate to make new neurons and provide a permissive environment for axon growth allowing spinal cord regeneration.

Having R-and NR-stages provides and ideal system to identify genes and proteins that promote or block regeneration. An extensive difference in the transcriptome and proteome deployed in response to injury in R and NR-stages was observed including differences in the response of genes related to neurogenesis and axonal growth cone; metabolism and mitochondrial homeostasis and immune response and inflammation.  Currently we are testing by gain and loss-of-function the role in spinal cord regeneration of a subset of genes and proteins identified by these global analyse. 

Key publications:

  • Spinal cord regeneration in Xenopuslaevis. Nat Protoc.; 12: 372-389, 2017.
  • The African clawed frog Xenopuslaevis: a model organism to study regeneration of the Central Nervous System. Neurosci Lett., 2016.
  • Regeneration of Xenopuslaevis spinal cord requires Sox2/3 expressing cells. Dev Biol., 2016. 


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