HYALURONAN IS A PREREQUISITE FOR DUCTAL BRANCHING MORPHOGENESIS

Hyaluronan, a macromolecular carbohydrate polymer of the extracellular matrix is prominent early in embryogenesis, coinciding with rapid tis sue growth. CD44, the predominant receptor for hyaluronan on vertebrat e cells, is a variably expressed transmembrane glycoprotein. Mouse ant erior prostate glands obtained at various postnatal time points were e xamined for the expression of hyaluronan and CD44. Reverse transcripta se polymerase chain reaction analysis was used to map the temporal reg ulation of specific CD44 variant isoforms, In each age group, hyaluron an was localized exclusively in the stromal matrix, Hyaluronan was gre atly reduced in the later ages and was entirely absent around the deve lopmentally quiescent proximal regions of the ducts, Early in prostate development, CD44 was prominent in the mesenchyme. However, in the la ter phases, CD44 expression became associated with membranes of epithe lial cells, The role of hyaluronan-CD44 interactions in ductal branchi ng morphogenesis was studied by serum-free organ culture of mouse ante rior prostate. In the presence of optimal levels of testosterone, the organs underwent ductal branching morphogenesis, Treatment with either neutralizing anti-CD44 antibodies, hyaluronan hexasaccharides or the enzyme hyaluronidase inhibited androgen-stimulated ductal branching mo rphogenesis, These results are suggestive of the significant role play ed by hyaluronan-CD44 interactions in mediating androgen-induced prost atic growth and morphogenesis.