Slit proteins prevent midline crossing and determine the dorsoventral position of major axonal pathways in the mammalian forebrain.
We report that Slit proteins, a family of secreted chemorepellents, are crucial for the proper development of several major forebrain tracts. Mice deficient in Slit2 and, even more so, mice deficient in both Slit1 and Slit2 show significant axon guidance errors in a variety of pathways, including corticofugal, callosal, and thalamocortical tracts. Analysis of multiple pathways suggests several generalizations regarding the functions of Slit proteins in the brain, which appear to contribute to (1) the maintenance of dorsal position by prevention of axonal growth into ventral regions, (2) the prevention of axonal extension toward and across the midline, and (3) the channeling of axons toward particular regions.
Bagri
Anil
A
Department of Anatomy, Howard Hughes Medical Institute, CA, USA.
Marín
Oscar
O
Plump
Andrew S
AS
Mak
Judy
J
Pleasure
Samuel J
SJ
Rubenstein
John L R
JL
Tessier-Lavigne
Marc
M
D000344:Afferent Pathways / Q000196:embryology; D000818:Animals; D001369:Axons / Q000502:physiology*; D002540:Cerebral Cortex / Q000196:embryology; D003337:Corpus Callosum / Q000196:embryology; D004298:Dopamine / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D008636:Mesencephalon / Q000196:embryology; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000502:physiology; D009412:Nerve Fibers / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009434:Neural Pathways / Q000196:embryology; D016548:Prosencephalon / Q000196:embryology*; D011971:Receptors, Immunologic / Q000378:metabolism; D012701:Serotonin / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D013687:Telencephalon / Q000196:embryology; D013788:Thalamus / Q000196:embryology; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
D004298:Dopamine; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D012701:Serotonin; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C120010:Slit1 protein, mouse