Article abstract
Nature Neuroscience 10, 712 - 719 (2007)
Published online: 7 May 2007 | doi:10.1038/nn1897
Identification of a lectin causing the degeneration of neuronal processes using engineered embryonic stem cells
Nicolas Plachta1, Christine Annaheim1, Stephanie Bissière2, Shuo Lin1, Markus Rüegg1, Sjouke Hoving3, Dieter Müller3, Françoise Poirier4, Miriam Bibel2 & Yves-Alain Barde1
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.
- Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
- Neuroscience Department, Novartis Institutes for Biomedical Research, CH-4002 Basel, Switzerland.
- Genome and Proteome Sciences Department, Novartis Institutes for Biomedical Research, CH-4002 Basel, Switzerland.
- Institut Jacques Monod, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7592, P6 and P7 Universities, Paris Cedex, France.
Correspondence to: Yves-Alain Barde1 e-mail: yves.barde@unibas.ch
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
Identification of IGFBP-6 as an effector of the tumor suppressor activity of SEMA3BOncogene Original Article
Retinal Discoloration TestJournal of Cerebral Blood Flow & Metabolism Brief Communication
Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injuryNature Neuroscience Article (01 Nov 2007)
See all 6 matches for Research
