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

J Nogueira-Rodrigues, SC Leite, R Pinto-Costa… - Developmental cell, 2022 - cell.com
J Nogueira-Rodrigues, SC Leite, R Pinto-Costa, SC Sousa, LL Luz, MA Sintra, R Oliveira…
Developmental cell, 2022cell.com
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 …
Summary
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.
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