RESTRICTED EXPRESSION OF THE HYALURONAN RECEPTOR, CD44, DURING POSTIMPLANTATION MOUSE EMBRYOGENESIS SUGGESTS KEY ROLES IN TISSUE FORMATION AND PATTERNING

CD44 is a multifunctional adhesion protein that acts as a major recept or for the hygroscopic extracellular matrix component, hyaluronan. Thi s 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 gro wth factors and thereby to promote cell attachment. During vertebrate development, multiple cases of hyaluronan involvement in cell prolifer ation, cell migration and histogenesis have been documented. In additi on, there is evidence suggesting a central role for cell surface glyco proteins and proteoglycans in mediating the action of polypeptide grow th factors involved in tissue patterning. In view of this, we undertoo k to investigate expression of the CD44 protein during postimplantatio n mouse embryogenesis. Between 9.5 and 12.5 days of embryonic developm ent, the predominant form of CD44 protein corresponds to the hyalurona n-binding CD44H form. However, species with a higher M(r) were also de tected, 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 t emporal and spatial distribution of this glycoprotein. CD44 is express ed at high levels in the heart, somites and condensing limb-bud mesenc hyme at critical stages of morphogenesis. These sites correlate with r egions where hyaluronan has been demonstrated to regulate morphogeneti c events. Of novel interest, however, is the high expression of CD44 i n regions that do not correlate with sites of known hyaluronan-mediate d developmental events. These include instructive epithelia participat ing in epithelial-mesenchymal cell interactions such as the apical ect odermal ridge of the developing limb bud and the odontogenic placodes of the presumptive upper and lower jaws.