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Identification of a lectin causing the degeneration of neuronal processes using engineered embryonic stem cells

Plachta, Nicolas, Annaheim, Christine, Bissière, Stephanie, Lin, Shuo, Rüegg, Markus, Hoving, Sjouke, Müller, Dieter, Poirier, Françoise, Bibel, Miriam and Barde, Yves-Alain ORCID: https://orcid.org/0000-0002-7627-461X 2007. Identification of a lectin causing the degeneration of neuronal processes using engineered embryonic stem cells. Nature Neuroscience 10 (6) , pp. 712-719. 10.1038/nn1897

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Abstract

Unlike the mechanisms involved in the death of neuronal cell bodies, those causing the elimination of processes are not well understood owing to the lack of suitable experimental systems. As the neurotrophin receptor p75NTR is known to restrict the growth of neuronal processes, we engineered mouse embryonic stem (ES) cells to express an Ngfr (p75NTR) cDNA under the control of the Mapt locus (the gene encoding tau), which begins to be active when ES cell–derived progenitors start elongating processes. This caused a progressive, synchronous degeneration of all processes, and a prospective proteomic analysis showed increased levels of the sugar-binding protein galectin-1 in the p75NTR-engineered cells. Function-blocking galectin-1 antibodies prevented the degeneration of processes, and recombinant galectin-1 caused the processes of wild-type neurons to degenerate first, followed by the cell bodies. In vivo, the application of a glutamate receptor agonist, a maneuver known to upregulate p75NTR, led to an increase in the amount of galectin-1 and to the degeneration of neurons and their processes in a galectin-1–dependent fashion. Section of the sciatic nerve also rapidly upregulated levels of p75NTR and galectin-1 in terminal Schwann cells, and the elimination of nerve endings was delayed at the neuromuscular junction of mice lacking Lgals1 (the gene encoding galectin-1). These results indicate that galectin-1 actively participates in the elimination of neuronal processes after lesion, and that engineered ES cells are a useful tool for studying relevant aspects of neuronal degeneration that have been hitherto difficult to analyze.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
ISSN: 1097-6256
Last Modified: 27 Oct 2022 08:26
URI: https://orca.cardiff.ac.uk/id/eprint/62286

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