Restricted expression of the hyaluronan receptor, CD44, during postimplantation mouse embryogenesis suggests key roles in tissue formation and patterning

ABSTRACT CD44 is a multifunctional adhesion protein that acts as a major receptor for the hygroscopic extracellular matrix component, hyaluronan. This receptor-ligand binding directly mediates at least some of the cell-cell and cell-matrix interactions ascribed to CD44. Other interactions involving CD44 may be modulated indirectly by its ability to bind growth factors and thereby to promote cell attachment. During vertebrate development, multiple cases of hyaluronan involvement in cell proliferation, cell migration and histogenesis have been documented. In addition, there is evidence suggesting a central role for cell surface glycoproteins and proteoglycans in mediating the action of polypeptide growth factors involved in tissue patterning. In view of this, we undertook to investigate expression of the CD44 protein during postimplantation mouse embryogenesis. Between 9.5 and 12.5 days of embryonic development, the pre-dominant form of CD44 protein corresponds to the hyaluronan-binding CD44H form. However, species with a higher Mr were also detected, implying that CD44 isoforms generated by alternative splicing of CD44 RNA are employed in normal development. Further, we used mouse embryos to perform whole-mount immunohistochemistry and examine the temporal and spatial distribution of this glycoprotein. CD44 is expressed at high levels in the heart, somites and condensing limb-bud mesenchyme at critical stages of morphogenesis. These sites correlate with regions where hyaluronan has been demonstrated to regulate morphogenetic events. Of novel interest, however, is the high expression of CD44 in regions that do not correlate with sites of known hyaluronan-mediated developmental events. These include instructive epithelia participating in epithelial-mesenchymal cell interactions such as the apical ectodermal ridge of the developing limb bud and the odontogenic placodes of the presumptive upper and lower jaws.