Accumulation of basement membrane-associated hyaluronate is reduced in the posterior neuropore region of mutant (curly tail) mouse embryos developing spinal neural tube defects.
We investigated the accumulation of newly synthesized glycoconjugates during spinal neurulation in mutant curly tail mouse embryos, a proportion of which develop lower spinal neural-tube defects (NTD). Embryos undergoing closure of the posterior neuropore (27- to 29-somite stage) were labeled in vitro with [3H]glucosamine, and [3H]glycoconjugates were analyzed by ion-exchange chromatography. Mutant embryos undergoing normal spinal neurulation exhibited a pattern of glycoconjugate accumulation closely similar to that observed for nonmutant embryos (Copp and Bernfield, 1988, Dev. Biol. 130, 573-582). Mutant embryos developing spinal NTD accumulated reduced amounts of [3H]hyaluronate specifically in the posterior neuropore region. Other embryonic regions and other glycoconjugates appeared unaffected by the developmental abnormality. Autoradiographic analysis of labeled curly tail embryos confirmed that [3H]hyaluronate accumulates in reduced amounts in the posterior neuropore region and indicated that this reduction is mainly localized to the site of developing basement membranes, beneath the neuroepithelium and around the notochord. Accumulation of [3H]hyaluronate in the interstitial mesenchymal matrix of the posterior neuropore region is not consistently affected in embryos developing spinal NTD. These results provide support for a role for basement-membrane hyaluronate in lower spinal neurulation.
Copp
A J
AJ
Imperial Cancer Research Fund, Department of Zoology, Oxford, United Kingdom.
Bernfield
M
M
D000818:Animals; D001345:Autoradiography; D001485:Basement Membrane / Q000378:metabolism*; D005109:Extracellular Matrix / Q000502:physiology; D005944:Glucosamine / Q000378:metabolism; D006001:Glycoconjugates / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D008817:Mice, Mutant Strains; D009436:Neural Tube Defects / Q000196:embryology*; D013116:Spinal Cord / Q000196:embryology* / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism
D006001:Glycoconjugates; D013431:Sulfates; D006820:Hyaluronic Acid; D005944:Glucosamine