Abstract
Rhythmic spontaneous electrical activity occurs in many parts of the developing nervous system, where it plays essential roles in the refinement of neural connections. By blocking or slowing this bursting activity, via in ovo drug applications at precise developmental periods, we show that such activity is also required at much earlier stages for spinal motoneurons to accurately execute their first major dorsal-ventral pathfinding decision. Blockade or slowing of rhythmic bursting activity also prevents the normal expression patterns of EphA4 and polysialic acid on NCAM, which may contribute to the pathfinding errors observed. More prolonged (E2-5) blockade resulted in a downregulation of LIM homeodomain transcription factors, but since this occurred only after the pathfinding errors and alterations in guidance molecules, it cannot have contributed to them.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Action Potentials / drug effects
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Action Potentials / genetics*
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Animals
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Cell Differentiation / drug effects
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Cell Differentiation / genetics*
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Cell Movement / drug effects
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Cell Movement / genetics
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Chick Embryo
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Down-Regulation / genetics
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GABA Antagonists / pharmacology
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Gene Expression Regulation, Developmental / genetics
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Growth Cones / drug effects
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Growth Cones / metabolism*
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Growth Cones / ultrastructure
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Motor Neurons / cytology
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Motor Neurons / drug effects
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Motor Neurons / metabolism*
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Muscle, Skeletal / embryology
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Muscle, Skeletal / innervation
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Nerve Growth Factors / metabolism*
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Neural Cell Adhesion Molecules / metabolism
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Neural Inhibition / drug effects
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Neural Inhibition / genetics
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Receptor, EphA4 / genetics
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Receptor, EphA4 / metabolism
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Receptors, Glycine / antagonists & inhibitors
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Receptors, Glycine / metabolism
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Sialic Acids / genetics
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Sialic Acids / metabolism
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Spinal Cord / cytology
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Spinal Cord / embryology*
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Spinal Cord / metabolism
Substances
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GABA Antagonists
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Homeodomain Proteins
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Nerve Growth Factors
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Neural Cell Adhesion Molecules
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Receptors, Glycine
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Sialic Acids
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polysialic acid
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Receptor, EphA4