Normal patterns of spontaneous activity are required for correct motor axon guidance and the expression of specific guidance molecules.
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.
Hanson
M Gartz
MG
Department of Neurosciences, Case School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Landmesser
Lynn T
LT
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002642:Chick Embryo; D015536:Down-Regulation / Q000235:genetics; D018756:GABA Antagonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000196:embryology / Q000294:innervation; D009414:Nerve Growth Factors / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics; D036122:Receptor, EphA4 / Q000235:genetics / Q000378:metabolism; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism; D012794:Sialic Acids / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism
D018756:GABA Antagonists; D018398:Homeodomain Proteins; D009414:Nerve Growth Factors; D019006:Neural Cell Adhesion Molecules; D018009:Receptors, Glycine; D012794:Sialic Acids; C021319:polysialic acid; D036122:Receptor, EphA4