Extension of long leading processes and neuronal migration in the mammalian brain directed by the chemoattractant netrin-1.
Long distance cell migration occurs throughout the developing CNS, but the underlying cellular and molecular mechanisms are poorly understood. We show that the directed circumferential migration of basilar pontine neurons from their origin in the neuroepithelium of the dorsal hindbrain to the ventral midline involves the extension of long (>1 mm) leading processes, which marker analyses suggest are molecularly distinct from axons. In vivo analysis of knockout mice implicates the axonal chemoattractant netrin-1, functioning via its receptor Deleted in Colorectal Cancer (DCC), in attracting the leading process to the ventral midline. Direct evidence for this chemoattractant mechanism is provided, using explant cultures and time-lapse analysis in vitro. Our results demonstrate the attraction of migrating neurons in the mammalian brain by an axon guidance molecule and the chemotactic responsiveness of their leading processes.
Yee
K T
KT
Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037, USA.
Simon
H H
HH
Tessier-Lavigne
M
M
O'Leary
D M
DM
D000818:Animals; D001921:Brain / Q000166:cytology* / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal; D002465:Cell Movement / Q000502:physiology; D058969:Contactin 2; D000075389:DCC Receptor; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D000075388:Netrin-1; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011149:Pons / Q000166:cytology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D012249:Rhombencephalon / Q000166:cytology / Q000502:physiology; D025521:Tumor Suppressor Proteins
D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D000075389:DCC Receptor; C501910:Dcc protein, mouse; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; C000617354:Ntn1 protein, rat; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1