L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation.
L1 is a cell adhesion molecule associated with axonal outgrowth and fasciculation during spinal cord development and may reiterate its developmental role in adults following injury; L1 is upregulated on certain sprouting and regenerating axons in adults, but it is unclear if L1 expression is necessary for, or contributes to, regrowth of axons. This study asks if L1 is required for small-diameter primary afferents to sprout by conducting unilateral dorsal rhizotomies (six segments; T10-L2) on both wild-type and L1 mutant mice. First we determined that L1 co-localizes substantially with the peptidergic (calcitonin gene-related peptide; CGRP) but minimally with the nonpeptidergic (isolectin B4; IB4) primary afferents in intact wild-type and L1 mutant mice. However, we encountered a complication using IB4 to identify primary afferents post-rhizotomy; we detected extensive abnormal IB4 expression in the dorsal horn and dorsal columns. Much of this aberrant IB4 labeling is associated with fibrous astrocytes and microglia. Five days after dorsal rhizotomy a large decrease in peptidergic and nonpeptidergic afferents is evident on the deafferented side in both wild-type and L1 mutants. Three months after surgery the peptidergic primary afferents sprouted into the center of the denervated dorsal horn in both wild-type and mutant mice, and quantitative analyses confirmed a sprouting density of similar magnitude in both genotypes. In contrast, we did not detect sprouting in the nonpeptidergic primary afferents in either genotype. These results suggest that the absence of L1 neither diminishes nor enhances sprouting of peptidergic small-diameter primary afferent axons following a dorsal rhizotomy.
Runyan
S A
SA
Department of Physiological Science, UCLA, Box 951606, Los Angeles, CA 90095-1606, USA.
Roy
R R
RR
Zhong
H
H
Phelps
P E
PE
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000502:physiology*; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D019051:Rhizotomy / Q000379:methods; D013126:Spinal Nerve Roots / Q000502:physiology*; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D037102:Lectins; D039842:Neural Cell Adhesion Molecule L1; D015740:Calcitonin Gene-Related Peptide