Toole B P, Munaim S I, Welles S, Knudson C B
Department of Anatomy and Cellular Biology, Tufts University Health Sciences Center, Boston, MA 02111.
Ciba Found Symp. 1989;143:138-45; discussion 145-9 281-5. doi: 10.1002/9780470513774.ch9.
Hyaluronate is a major component of the intercellular matrix surrounding proliferating and migrating cells in embryonic tissues. When placed in culture, mesodermal cells from the early, proliferative stages of limb development produce high levels of hyaluronate and exhibit prominent hyaluronate-dependent pericellular coats. Cells from the subsequent stages of mesodermal condensation that precede differentiation to cartilage and muscle produce less hyaluronate and do not exhibit these coats. Also at this time, binding sites specific for hyaluronate appear on the surface of the mesodermal cells. These binding sites may participate in the mechanism of condensation by mediating cell aggregation and the endocytosis of hyaluronate. Further changes in hyaluronate-cell interaction occur during differentiation of the condensed mesoderm to cartilage and muscle. Hyaluronate synthesis and pericellular coat formation in the mesoderm are stimulated by a factor, related to transforming growth factor-beta, that is produced by the surrounding ectoderm. The early limb also contains high levels of basic fibroblast growth factor. Its concentration is highest at the earliest stages, when cell proliferation and hyaluronate synthesis are prominent activities, and this factor has been shown to stimulate both these activities in cultures of limb mesodermal cells. Thus fibroblast growth factor and transforming growth factor-beta may be important in the regulation of early growth and morphogenesis of the limb.
透明质酸盐是胚胎组织中围绕增殖和迁移细胞的细胞外基质的主要成分。在培养时，来自肢体发育早期增殖阶段的中胚层细胞会产生高水平的透明质酸盐，并呈现出显著的依赖透明质酸盐的细胞周被膜。来自中胚层凝聚后续阶段、在分化为软骨和肌肉之前的细胞产生的透明质酸盐较少，且不呈现这些被膜。同样在这个时候，中胚层细胞表面会出现对透明质酸盐特异的结合位点。这些结合位点可能通过介导细胞聚集和透明质酸盐的内吞作用参与凝聚机制。在凝聚的中胚层分化为软骨和肌肉的过程中，透明质酸盐 - 细胞相互作用会发生进一步变化。中胚层中的透明质酸盐合成和细胞周被膜形成受到一种与转化生长因子 -β 相关的因子的刺激，该因子由周围的外胚层产生。早期肢体中还含有高水平的碱性成纤维细胞生长因子。其浓度在最早阶段最高，此时细胞增殖和透明质酸盐合成是突出的活动，并且已表明该因子在肢体中胚层细胞培养物中能刺激这两种活动。因此，成纤维细胞生长因子和转化生长因子 -β 可能在肢体早期生长和形态发生的调节中起重要作用。
