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Updated: Aug 6, 2026
Whole-mount Imaging of Mouse Embryo Sensory Axon Projections
Published on: December 9, 2014
Analysis of the L1-deficient mouse phenotype reveals cross-talk between Sema3A and L1 signaling pathways in axonal
V Castellani1, A Chédotal, M Schachner
1Laboratoire de Génétique et Physiologie du Développement, UMR 6545 CNRS, IBDM, Marseille, France.
Abstract:
In humans, defects of the corticospinal tract have been attributed to mutations in the gene encoding L1 CAM, a phenotype that is reproduced in L1-deficient mice. Using coculture assays, we report that Sema3A secreted from the ventral spinal cord repels cortical axons from wild-type but not from L1-deficient mice. L1 and neuropilin-1 (NP-1) form a stable complex, and their extracellular domains can directly associate. Thus, L1 is a component of the Sema3A receptor complex, and L1 mutations may disrupt Sema3A signaling in the growth cone, leading to guidance errors. Addition of soluble L1Fc chimeric molecules does not restore Sema3A responsiveness of L1-deficient axons; instead, it converts the repulsion of wild-type axons into an attraction, further supporting a function for L1 in the Sema3A transducing pathways within the growth cone.
Insights
Neural development relies on L1 cell adhesion molecule (L1 CAM) for proper corticospinal tract formation. L1 CAM acts as a crucial component of the Semaphorin 3A (Sema3A) receptor complex, guiding axonal growth.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Mutations in L1 cell adhesion molecule (L1 CAM) gene cause corticospinal tract defects in humans.
- L1-deficient mice exhibit a similar phenotype, indicating L1 CAM's role in neural development.
Purpose of the Study:
- To investigate the role of L1 CAM in the repulsive guidance of cortical axons by Semaphorin 3A (Sema3A).
- To determine if L1 CAM is part of the Sema3A receptor complex.
Main Methods:
- Coculture assays were performed using wild-type and L1-deficient mouse cortical neurons.
- Analysis of L1 CAM and neuropilin-1 (NP-1) complex formation.
- Experiments with soluble L1Fc chimeric molecules.
Main Results:
- Sema3A repelled wild-type cortical axons but not L1-deficient axons in coculture assays.
- L1 CAM and NP-1 form a stable complex, with direct extracellular domain association.
- Soluble L1Fc converted Sema3A repulsion of wild-type axons into attraction.
Conclusions:
- L1 CAM is a component of the Sema3A receptor complex, essential for mediating Sema3A-induced axonal repulsion.
- L1 CAM mutations disrupt Sema3A signaling in growth cones, leading to guidance errors.
- L1 CAM plays a critical role in the intracellular signaling pathways that regulate axonal guidance.
