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  • Rewired glycosylation activity promotes scarless regeneration and functional recovery in spiny mice after complete spinal cord transection.

Rewired glycosylation activity promotes scarless regeneration and functional recovery in spiny mice after complete spinal cord transection.

Developmental cell (2022-01-06)
Joana Nogueira-Rodrigues, Sérgio C Leite, Rita Pinto-Costa, Sara C Sousa, Liliana L Luz, Maria A Sintra, Raquel Oliveira, Ana C Monteiro, Gonçalo G Pinheiro, Marta Vitorino, Joana A Silva, Sónia Simão, Vitor E Fernandes, Jan Provazník, Vladimir Benes, Célia D Cruz, Boris V Safronov, Ana Magalhães, Celso A Reis, Jorge Vieira, Cristina P Vieira, Gustavo Tiscórnia, Inês M Araújo, Mónica M Sousa
ABSTRACT

Regeneration of adult mammalian central nervous system (CNS) axons is abortive, resulting in inability to recover function after CNS lesion, including spinal cord injury (SCI). Here, we show that the spiny mouse (Acomys) is an exception to other mammals, being capable of spontaneous and fast restoration of function after severe SCI, re-establishing hind limb coordination. Remarkably, Acomys assembles a scarless pro-regenerative tissue at the injury site, providing a unique structural continuity of the initial spinal cord geometry. The Acomys SCI site shows robust axon regeneration of multiple tracts, synapse formation, and electrophysiological signal propagation. Transcriptomic analysis of the spinal cord following transcriptome reconstruction revealed that Acomys rewires glycosylation biosynthetic pathways, culminating in a specific pro-regenerative proteoglycan signature at SCI site. Our work uncovers that a glycosylation switch is critical for axon regeneration after SCI and identifies β3gnt7, a crucial enzyme of keratan sulfate biosynthesis, as an enhancer of axon growth.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Bovine Serum Albumin, heat shock fraction, protease free, pH 7, ≥98%
Sigma-Aldrich
Collagenase from Clostridium histolyticum, 0.2 μm filtered, suitable for release of physiologically active rat hepatocytes, Type IV-S, 0.5-5.0 FALGPA units/mg solid, ≥125 CDU/mg solid
Sigma-Aldrich
Trichrome Stain (Masson) Kit
Sigma-Aldrich
Donkey serum
Sigma-Aldrich
Gelatin from cold water fish skin, solid
Sigma-Aldrich
Endo-β-Galactosidase, Bacteroides fragilis, Recombinant, E. coli, Endo-β-Galactosidase, Bacteroides fragilis, Recombinant, E. coli, hydrolyzes internal β-galactosidic linkages of oligosaccharides in poly-N-acetyl-lactosamine structures.