Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve.
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.
Schwarz
Quenten
Q
Department of Cell Biology, Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom.
Gu
Chenghua
C
Fujisawa
Hajime
H
Sabelko
Kimberly
K
Gertsenstein
Marina
M
Nagy
Andras
A
Taniguchi
Masahiko
M
Kolodkin
Alex L
AL
Ginty
David D
DD
Shima
David T
DT
Ruhrberg
Christiana
C
D000818:Animals; D001369:Axons; D019521:Body Patterning; D002451:Cell Compartmentation; D002465:Cell Movement; D005154:Facial Nerve / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008024:Ligands; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020033:Protein Isoforms; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology; D040121:Semaphorin-3A / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D008024:Ligands; D020033:Protein Isoforms; D040121:Semaphorin-3A; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1