Common pattern of CD44 isoforms is expressed in morphogenetically active epithelia

CD44 is a widely distributed cell surface glycoprotein that is expressed as many isoforms arising from a single gene by alternative splicing. An important ligand for the widespread CD44 isoform, CD44s (standard form of CD44), is hyaluronan but ligands for the numerous variant isoforms are not as well characterized. Although it has been documented that CD44 is present at critical sites and stages of morphogenesis of several organs, the nature of the isoforms expressed and their precise localization have not been described. In this study we have determined the identity and distribution of CD44 isoforms expressed during development of several embryonic mouse organs by a combination of immunohistochemistry, in situ hybridization, reverse transcription-polymerase chain reaction, and DNA sequencing. As expected from previous studies, numerous CD44 variants are expressed by actively proliferating and invaginating epithelia at sites of epithelial-mesenchymal interaction, e.g., in the developing tooth, nose and hair follicle. Our results show that most prominent amongst these variants at these sites are CD44(v3v10), CD44(v4-v10), and CD44(v6-v10), as was also found previously in the apical ectodermal ridge of the developing limb (Yu et al. [19961). The common pattern of expression of these three particular variants in active epithelia implies that they play an important role in morphogenesis. Also very prominent in morphogenetically active epithelia is CD44s; hyaluronan is uniformly absent from these epithelia and often also from associated mesenchyme with which they interact, supporting the previously documented role of CD44s in endocytic removal of hyaluronan.