Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Afferent Pathways / embryology
-
Animals
-
Axons / physiology*
-
Cerebral Cortex / embryology
-
Corpus Callosum / embryology
-
Dopamine / physiology
-
Embryonic and Fetal Development / physiology
-
Intercellular Signaling Peptides and Proteins
-
Mesencephalon / embryology
-
Mice
-
Mice, Mutant Strains
-
Mutation / physiology
-
Nerve Fibers / physiology
-
Nerve Tissue Proteins / genetics
-
Nerve Tissue Proteins / physiology*
-
Neural Pathways / embryology
-
Prosencephalon / embryology*
-
Receptors, Immunologic / metabolism
-
Roundabout Proteins
-
Serotonin / physiology
-
Synaptic Transmission / physiology
-
Telencephalon / embryology
-
Thalamus / embryology
Substances
-
Intercellular Signaling Peptides and Proteins
-
Nerve Tissue Proteins
-
Receptors, Immunologic
-
Slit1 protein, mouse
-
Serotonin
-
Slit homolog 2 protein
-
Dopamine