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RESEARCH PAPER

Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve

¹ Department of Cell Biology, Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom; ² Department of Neuroscience and ³ Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; ⁴ Group of Developmental Neurobiology, Division of Biological Science, Nagoya University Graduate School of Science, Chikusa-ku, Nagoya 464-8602, Japan; ⁵ Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA; ⁶ Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada; ⁷ Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; ⁸ Eyetech Pharmaceuticals Inc., Woburn, Massachusetts 01801, USA

Developing neurons accurately position their somata within the neural tube to make contact with appropriate neighbors and project axons to their preferred targets. Taking advantage of a collection of genetically engineered mouse mutants, we now demonstrate that the behavior of somata and axons of the facial nerve is regulated independently by two secreted ligands for the transmembrane receptor neuropilin 1 (Nrp1), the semaphorin Sema3A and the VEGF164 isoform of Vascular Endothelial Growth Factor. Although Sema3A is known to control the guidance of facial nerve axons, we now show that it is not required for the pathfinding of their somata. Vice versa, we find that VEGF164 is not required for axon guidance of facial motor neurons, but is essential for the correct migration of their somata. These observations demonstrate, for the first time, that VEGF contributes to neuronal patterning in vivo, and that different compartments of one cell can be co-ordinately patterned by structurally distinct ligands for a shared receptor.

[Keywords: Neuronal migration; axon guidance; neuropilin; VEGF; semaphorins]

Received May 16, 2004; revised version accepted September 13, 2004.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.322904.

⁹ Corresponding author. E-MAIL c.ruhrberg{at}ucl.ac.uk; FAX 44-0-207-608-6810.

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