GLYCOCONJUGATES IN NORMAL AND ABNORMAL SECONDARY NEURULATION

In chick embryos, the anterior greater portion of the neural tube deve lops by the folding, apposition, and fusion of the neuroectoderm. The smaller caudal portion that forms the secondary neural tube (lumbosacr al and coccygeal regions) is derived from the tail bud, an aggregate o f mesenchymal cells located at the caudal limit of the body. Tail bud mesenchyme, arranged in a solid cord, undergoes mesenchymal-epithelial transformation to form the secondary neural tube. Previous evidence s uggests that this transformation is accompanied by modulation of cell surface glycoconjugates in the differentiating tissues. In this study, we show by lectin histochemistry and lectin blotting of proteins isol ated by SDS-PAGE, that Datura stramonium agglutinin (DSA) binds prefer entially to differentiating tail bud cells. This lectin is specific fo r beta 1-4-linked N-acetylglycosamine oligomers, such as the oligosacc harides of the poly-N-acetyllactosamine series that have been previous ly implicated in cell differentiation. Ultrastructural lectin cytochem istry indicates that at least some of the proteins binding DSA are loc alized extracellularly. The use of DSA as a teratogen resulted in embr yos showing a variety of neural tube and notochord defects. We have al so examined the binding of DSA to embryos that were treated with terat ogenic doses of retinoic acid by sub-blastodermal injection, and find that the DSA-binding patterns are perturbed. Analysis of DSA-treated e mbryos using the TUNEL technique indicated that cell death was not a f actor in DSA teratogenesis. This strongly suggests that the glycoconju gates of the cell surface have a role in the normal differentiation of tail bud mesenchyme into the neuroepithelium of the secondary neural tube. Perturbations of glycoconjugate activity results in defects of t he secondary neural tube and associated tail bud derivatives. (C) 1995 Wiley-Liss, Inc.