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Development 128, 3963-3974 (2001)
© 2001 The Company of Biologists Limited

RET signaling is essential for migration, axonal growth and axon guidance of developing sympathetic neurons

Hideki Enomoto1, Peter A. Crawford1, Alexander Gorodinsky1, Robert O. Heuckeroth2,3, Eugene M. Johnson, Jr.3 and Jeffrey Milbrandt1,*

1 Departments of Pathology and Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, Box 8118, St Louis, MO 63110, USA
2 Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, Box 8116, St Louis, MO 63110, USA
3 Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8113, St Louis, MO 63110, USA

*Author for correspondence (e-mail: jeff{at}pathbox.wustl.edu)

Accepted July 26, 2001

Sympathetic axons use blood vessels as an intermediate path to reach their final target tissues. The initial contact between differentiating sympathetic neurons and blood vessels occurs following the primary sympathetic chain formation, where precursors of sympathetic neurons migrate and project axons along or toward blood vessels. We demonstrate that, in Ret-deficient mice, neuronal precursors throughout the entire sympathetic nervous system fail to migrate and project axons properly. These primary deficits lead to mis-routing of sympathetic nerve trunks and accelerated cell death of sympathetic neurons later in development. Artemin is expressed in blood vessels during periods of early sympathetic differentiation, and can promote and attract axonal growth of the sympathetic ganglion in vitro. This analysis identifies RET and artemin as central regulators of early sympathetic innervation.

Key words: Ret, Knockout mouse, Sympathetic neuron, Axon growth, Axon guidance, Migration




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© The Company of Biologists Ltd 2001