Urethral seam formation and hypospadias

Citation
Ls. Baskin et al., Urethral seam formation and hypospadias, CELL TIS RE, 305(3), 2001, pp. 379-387
Citations number
25
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL AND TISSUE RESEARCH
ISSN journal
0302-766X → ACNP
Volume
305
Issue
3
Year of publication
2001
Pages
379 - 387
Database
ISI
SICI code
0302-766X(200109)305:3<379:USFAH>2.0.ZU;2-4
Abstract
Knowledge of the formation of the normal male urethra may elucidate the eti ology of hypospadias. We describe urethral formation in the mouse, show the similarities and relevance to human urethral development, and introduce th e concept of the epithelial seam formation and remodeling during urethral f ormation. Three mechanisms may account for epithelial seam formation: (1) e pithelial-mesenchymal transformation similar to that described in the fusio n of the palatal shelves, (2) apoptosis, and/or (3) tissue remodeling via c ellular migration. Urethral development in the embryonic mouse (14-21 days of gestation) was compared with urethral formation in embryonic human speci mens (8-16 weeks of gestation) by using histology, immunohistochemistry, an d three-dimensional reconstruction. The urethra forms by fusion of the epit helial edges of the urethral folds, giving a midline epithelial seam. The e pithelial seam is remodeled via cellular migration into a centrally located urethra and ventrally displaced remnant of epithelial cells. The epithelia l seam is remodeled by narrowing approximately at its midpoint, with subseq uent epithelial migration into the urethra or penile skin. The epithelial c ells are replaced by mesenchymal cells. This remodeling seam displays a nar row band (approximately 30 mum wide) of apoptotic activity corresponding to the mesenchymal cells and not to epithelial cells. No evidence was seen of the co-expression of cytokeratin and mesenchymal markers (actin or vimenti n). Urethral seam formation occurs in both the mouse and the human. Our dat a in the mouse support the hypothesis that seam transformation occurs via c ellular migration and not by epithelial mesenchymal transformation or epith elial apoptosis. We postulate that disruption of epithelial fusion, remodel ing, and cellular migration leads to hypospadias.