Mis-expression of L1 on pre-crossing spinal commissural axons disrupts pathfinding at the ventral midline.
In vertebrates, spinal commissural axons project along a transverse path toward and across the floor plate (FP). Post-crossing commissural axons alter their responsiveness to FP-associated guidance cues and turn to project longitudinally in a fasciculated manner prior to extending away from the midline. The upregulation of the neural cell adhesion molecule L1 on crossed commissural axon segments has been proposed to facilitate pathfinding on the contralateral side of the FP. To explore this possibility in vivo, we used Math1 regulatory sequences to target L1 to commissural axons before they cross the ventral midline. L1 mis-expression did not alter the distribution of commissural axon-associated markers or the ventral extension of commissural axons toward the midline. However, commissural axons often stalled or inappropriately projected into the longitudinal plane at the ipsilateral FP margin. These observations suggest that L1-mediated pathfinding decisions are normally delayed until axons have crossed the ventral midline (VM).
Imondi
Ralph
R
Department of Neuroscience, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Bronx, NY 10461, USA.
Jevince
Angela R
AR
Helms
Amy W
AW
Johnson
Jane E
JE
Kaprielian
Zaven
Z
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D003463:Cues; D007839:Functional Laterality / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018390:Gene Targeting / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000378:metabolism*; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D039842:Neural Cell Adhesion Molecule L1; D016875:tau Proteins; C500943:Atoh1 protein, mouse