Epithelial-mesenchymal interactions in development of the mouse fetal genital tubercle

Epithelial-mesenchymal interactions play a central role in the development of urogenital organs. We hypothesized that normal development of the extern al genitalia depends upon proper mesenchymal-epithelial signaling. The mese nchyme of the adult mouse penis consists of a corpus cavernosum and proxima l and distal bones. The differentiation of penile mesenchyme into bone and cartilage begins after birth and can be accelerated by androgens. After det ermining the sex, genital tubercles of fetal mice at gestational day 15 wer e removed. The genital tubercles were trypsinized and microdissected to rem ove the epidermis and urethra from the mesenchyme. Recombinant specimens we re created by combining genital tubercle mesenchyme with genital tubercle e pithelium, bladder epithelium or tail epidermis. Tissues were grafted under the renal capsule of male athymic mice. After 3 weeks of growth, grafts we re removed from the kidney, weighed and stained with hematoxylin and eosin, Alcian blue and peanut agglutinin. Male and female grafts showed no differ ence in growth or differentiation. Intact grafts and recombinant grafts, ir respective of the epithelial source, grew significantly more than grafts of the mesenchyme only. Recombinant grafts demonstrated a significantly highe r prevalence of cartilage formation and mesenchymal differentiation compare d to grafts of the mesenchyme without epithelium. Since heterologous epithe lium is able to induce equivalent growth and differentiation of phallic mes enchyme, epithelium carries a permissive, but critical, role in genital mes enchyme development.