Mis-expression of L1 on pre-crossing spinal commissural axons disrupts pathfinding at the ventral midline

• Published in: Molecular and cellular neuroscience Vol. 36; no. 4; pp. 462 - 471
• Main Authors: Imondi, Ralph, Jevince, Angela R., Helms, Amy W., Johnson, Jane E., Kaprielian, Zaven
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2007
• Subjects: Altered responsiveness; Animals; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Cell Differentiation - physiology; Commissural axon; Cues; Fasciculation; Floor plate; Functional Laterality - physiology; Gene Expression Regulation, Developmental - genetics; Gene Targeting - methods; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Growth Cones - metabolism; Growth Cones - ultrastructure; Math1; Mice; Mice, Transgenic; Neural Cell Adhesion Molecule L1 - genetics; Neural Cell Adhesion Molecule L1 - metabolism; Neural Pathways - cytology; Neural Pathways - embryology; Neural Pathways - metabolism; Spinal Cord - cytology; Spinal Cord - embryology; Spinal Cord - metabolism; tau Proteins - genetics; tau Proteins - metabolism; Up-Regulation - physiology; Math1; Floor plate; Commissural axon; L1; Altered responsiveness; Fasciculation
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2007.08.003

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).