N-CAM alterations in splotch neural tube defect mouse embryos.
The splotch (Sp) mouse is a model for both neurulation defects and defects in neural crest cell (NCC) derivatives. Since neurulation and NCC emigration from the neural tube occur at similar times in development, we suggest that these two events share a mechanism that, if disrupted, leads to malformations in both developmental pathways. Previous studies have shown that the underlying defect in these mutants may involve a mechanism that alters cellular organization and communication. Cell adhesion molecules (CAMs) have been linked with such interactions and because some, including N-CAM, are involved in neural development, we were interested in their pattern of expression in the splotch mutant. Immunolocalization studies showed similar temporospatial distributions of N-CAM antibody in embryonic day 9 mutants and controls. However, mutant embryos had a much higher intensity of anti-N-CAM fluorescence compared to controls. Further characterization using immunoblot analysis revealed that Sp mutants have an altered N-CAM polypeptide profile. Two N-CAM isoforms (Mr 140K and 180K, K = 10(3] are normally present at this time of development. However, extracts from Sp embryos display a heavier N-CAM species (Mr 200K), as well as an altered 140K isoform. Heterozygotes also exhibit a different N-CAM profile, displaying a band between 180K and 200K in addition to the normal 180K and 140K species. Microheterogeneity was also observed in mutant and heterozygous embryos carrying Spd, an allele of Sp. However, these differences were less dramatic than that of Sp. The Sp locus may be involved in post-translational modification of N-CAM. An aberration in N-CAM processing could be the primary target of the mutation that leads to the development abnormalities observed in this mouse mutant.
Moase
C E
CE
Department of Biology, McGill University, Montréal, Québec, Canada.
Trasler
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DG
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D009432:Neural Crest / Q000378:metabolism*; D009436:Neural Tube Defects / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal