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Invariant Sema5A inhibition serves an ensheathing function during optic nerve development.
- Source :
-
Development (Cambridge, England) [Development] 2003 Feb; Vol. 130 (4), pp. 775-84. - Publication Year :
- 2003
-
Abstract
- Retinal axon pathfinding from the retina into the optic nerve involves the growth promoting axon guidance molecules L1, laminin and netrin 1, each of which governs axon behavior at specific regions along the retinal pathway. In identifying additional molecules regulating this process during embryonic mouse development, we found that transmembrane Semaphorin5A mRNA and protein was specifically expressed in neuroepithelial cells surrounding retinal axons at the optic disc and along the optic nerve. Given that growth cone responses to a specific guidance molecule can be altered by co-exposure to a second guidance cue, we examined whether retinal axon responses to Sema5A were modulated by other guidance signals axons encountered along the retinal pathway. In growth cone collapse, substratum choice and neurite outgrowth assays, Sema5A triggered an invariant inhibitory response in the context of L1, laminin, or netrin 1 signaling, suggesting that Sema5A inhibited retinal axons throughout their course at the optic disc and nerve. Antibody-perturbation studies in living embryo preparations showed that blocking of Sema5A function led to retinal axons straying out of the optic nerve bundle, indicating that Sema5A normally helped ensheath the retinal pathway. Thus, development of some CNS nerves requires inhibitory sheaths to maintain integrity. Furthermore, this function is accomplished using molecules such as Sema5A that exhibit conserved inhibitory responses in the presence of co-impinging signals from multiple families of guidance molecules.
- Subjects :
- Animals
Antibodies, Monoclonal pharmacology
Axons drug effects
Axons physiology
Gene Expression Regulation, Developmental
Growth Cones physiology
In Vitro Techniques
Laminin metabolism
Membrane Proteins genetics
Mice
Mice, Inbred Strains
Nerve Growth Factors metabolism
Nerve Tissue Proteins genetics
Netrin-1
Optic Nerve physiology
Protein Structure, Tertiary
Recombinant Proteins genetics
Recombinant Proteins metabolism
Retina drug effects
Retina embryology
Retina physiology
Semaphorins
Signal Transduction
Thrombospondins genetics
Thrombospondins metabolism
Tumor Suppressor Proteins
Membrane Proteins metabolism
Nerve Tissue Proteins metabolism
Optic Nerve embryology
Subjects
Details
- Language :
- English
- ISSN :
- 0950-1991
- Volume :
- 130
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 12506007
- Full Text :
- https://doi.org/10.1242/dev.00299