Reelin Promotes Peripheral Synapse Elimination and Maturation

Carlo C. Quattrocchi,^1,2,7 Cheng Huang,^2,8 Sanyong Niu,^1,2 Michael Sheldon,^2,8 David Benhayon,⁹ Joiner Cartwright, Jr.,³ Dennis R. Mosier,^4,10 Flavio Keller,¹¹ Gabriella D'Arcangelo^1,2,5,6*

Abstract: Reelin is an extracellular protein that is crucial for layer formation in the embryonic brain. Here, we demonstrate that Reelin functions postnatally to regulate the development of the neuromuscular junction. Reelin is required for motor end-plate maturation and proper nerve-muscle connectivity, and it directly promotes synapse elimination. Unlike layer formation, neuromuscular junction development requires a function of Reelin that is not mediated by Disabled1 or very-low-density lipoprotein receptors and apolipoprotein E receptor 2 receptors but by a distinct mechanism involving its protease activity.

¹ The Cain Foundation Laboratories, Houston, TX 77030, USA.
² Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
³ Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
⁴ Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
⁵ Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
⁶ Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
⁷ Program in Neuroscience, Università degli Studi di Brescia, Brescia 25123, Italy.
⁸ Division of Hematology-Oncology and Texas Children's Cancer Center, Houston, TX 77030, USA.
⁹ Department of Anatomy and Neurobiology, University of Tennessee, Memphis, TN 38163, USA.
¹⁰ Veterans Administration Medical Center, Houston, TX 77030, USA.
¹¹ Laboratory of Developmental Neuroscience and Neural Plasticity, Università Campus Bio-Medico, Roma 00155, Italy.

^* To whom correspondence should be addressed. E-mail: gangelo{at}bcm.tmc.edu

Commentary: Study of the Neurobehavioral Consequences of Childhood Cancer: Entering the Genomic Era?.

P. Brouwers (2005)
J. Pediatr. Psychol. 30, 79-84
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Activity-Dependent Synaptic Competition at Mammalian Neuromuscular Junctions.

M. Buffelli, G. Busetto, C. Bidoia, M. Favero, and A. Cangiano (2004)
Physiology 19, 85-91
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Retraction.

C. C. Quattrocchi, C. Huang, S. Niu, M. Sheldon, D. Benhayon, J. Cartwright Jr., D. R. Mosier, F. Keller, and G. D'Arcangelo (2004)
Science 303, 1974b
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Comment on "Reelin Promotes Peripheral Synapse Elimination and Maturation".

C. Bidoia, T. Misgeld, E. Weinzierl, M. Buffelli, G. Feng, A. Cangiano, J. W. Lichtman, and J. R. Sanes (2004)
Science 303, 1977b
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Response to Comment on "Reelin Promotes Peripheral Synapse Elimination and Maturation".

G. D'Arcangelo (2004)
Science 303, 1977c
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The Central Fragment of Reelin, Generated by Proteolytic Processing In Vivo, Is Critical to Its Function during Cortical Plate Development.

Y. Jossin, N. Ignatova, T. Hiesberger, J. Herz, C. Lambert de Rouvroit, and A. M. Goffinet (2004)
J. Neurosci. 24, 514-521
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Is Reelin the Answer to Synapse Elimination at the Neuromuscular Junction?.

B. Chih and P. Scheiffele (2003)
Sci. STKE 2003, pe45
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