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The Journal of Neuroscience, September 3, 2008, 28(36):8993-9001; doi:10.1523/JNEUROSCI.0720-08.2008

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Development/Plasticity/Repair
Lysosomal Activity Associated with Developmental Axon Pruning

Jae W. Song,¹ Thomas Misgeld,² Hyuno Kang,¹ Sharm Knecht,³ Ju Lu,¹ Yi Cao,⁴ Susan L. Cotman,⁴ Derron L. Bishop,³ and Jeff W. Lichtman¹

¹Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, ²Institute of Neuroscience, Technical University Munich, 80802 Munich, Germany, ³Department of Medical Education, Indiana University School of Medicine–Muncie, Muncie, Indiana 47306, and ⁴Molecular Neurogenetics Unit and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114

Correspondence should be addressed to Jeff W. Lichtman, Department of Molecular and Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138. Email: jeff{at}mcb.harvard.edu

Clearance of cellular debris is a critical feature of the developing nervous system, as evidenced by the severe neurological consequences of lysosomal storage diseases in children. An important developmental process, which generates considerable cellular debris, is synapse elimination, in which many axonal branches are pruned. The fate of these pruned branches is not known. Here, we investigate the role of lysosomal activity in neurons and glia in the removal of axon branches during early postnatal life. Using a probe for lysosomal activity, we observed robust staining associated with retreating motor axons. Lysosomal function was involved in axon removal because retreating axons were cleared more slowly in a mouse model of a lysosomal storage disease. In addition, we found lysosomal activity in the cerebellum at the time of, and at sites where, climbing fibers are eliminated. We propose that lysosomal activity is a central feature of synapse elimination. Moreover, staining for lysosomal activity may serve as a marker for regions of the developing nervous system undergoing axon pruning.

Key words: synapse elimination; lysosome; autophagy; degradation; axon pruning; retraction bulb

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Received Feb. 15, 2008; revised July 15, 2008; accepted July 21, 2008.

Correspondence should be addressed to Jeff W. Lichtman, Department of Molecular and Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138. Email: jeff{at}mcb.harvard.edu

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