Abstract
We investigated the roles of netrin-1 and slit-2 in regulation and navigation of dopamine (DA) axon growth using an explant culture preparation of embryonic ventral midbrain (embryonic day 14) and a co-culture system. We found that netrin-1 protein significantly enhanced DA axonal outgrowth and promoted DA axonal outgrowth in a co-culture system of netrin-1 expressing cells. Such effects were mediated by the receptor DCC as demonstrated by antibody perturbation of the DCC receptor. In contrast, slit-2 inhibited DA neuron extensions and repelled DA neurite growth. These slit-2 activities required robo receptors since the reduced neurite extension was abolished by addition of excess robo receptors. In this system, netrin-1 stimulated and slit-2 opposed DA neurite growth. Such regulation may be important for DA axonal maintenance, regeneration, and phenotypic target recognition.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Cell Adhesion Molecules / metabolism
-
Cell Differentiation / drug effects
-
Cell Differentiation / physiology*
-
Cell Line
-
Cells, Cultured
-
DCC Receptor
-
Dopamine / metabolism*
-
G Protein-Coupled Inwardly-Rectifying Potassium Channels
-
Growth Cones / metabolism
-
Growth Inhibitors / metabolism
-
Growth Substances / metabolism
-
Humans
-
Intercellular Signaling Peptides and Proteins
-
Mesencephalon / cytology
-
Mesencephalon / embryology*
-
Mesencephalon / metabolism
-
Nerve Growth Factors / metabolism*
-
Nerve Growth Factors / pharmacology
-
Nerve Tissue Proteins / metabolism*
-
Nerve Tissue Proteins / pharmacology
-
Netrin-1
-
Neurites / drug effects
-
Neurites / metabolism*
-
Neurites / ultrastructure
-
Potassium Channels, Inwardly Rectifying / metabolism
-
Rats
-
Rats, Sprague-Dawley
-
Receptors, Cell Surface
-
Receptors, Immunologic / metabolism
-
Substantia Nigra / cytology
-
Substantia Nigra / embryology*
-
Substantia Nigra / metabolism
-
Tumor Suppressor Proteins / metabolism*
-
Tumor Suppressor Proteins / pharmacology
-
Tyrosine 3-Monooxygenase / metabolism
Substances
-
Cell Adhesion Molecules
-
DCC Receptor
-
DCC protein, human
-
G Protein-Coupled Inwardly-Rectifying Potassium Channels
-
Growth Inhibitors
-
Growth Substances
-
Intercellular Signaling Peptides and Proteins
-
NTN1 protein, human
-
Nerve Growth Factors
-
Nerve Tissue Proteins
-
Ntn1 protein, rat
-
Potassium Channels, Inwardly Rectifying
-
ROBO2 protein, human
-
Receptors, Cell Surface
-
Receptors, Immunologic
-
Tumor Suppressor Proteins
-
Netrin-1
-
Tyrosine 3-Monooxygenase
-
Slit homolog 2 protein
-
Dopamine