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We have described the basic development of the urethra including the two-zipper hypothesis of urethral development.   The human male urethra appears to form by two mechanisms: (1) An initial “opening zipper” that facilitates distal canalization of the solid urethral plate to form the urethral groove,  (androgen independent) and (2) A “closing zipper” facilitating fusion of the two epithelial surfaces of the urethral groove, and thus extending the penile urethra distally (androgen dependent). 

 
 
   
   


 

We have also described the “endodermal theory of urethral development in which the urethra is an extension of the bladder and grows out to the perineum replacing the classic ectodermal ingrowth theory (skin ingrowth). We have also showed the importance of epithelial mesenchymal interactions in development of the genital tubercle.

 
 

Li Y, Sinclair A, Cao M, Shen J, Choudhry S, Cunha G, et al. Canalization of The Urethral Plate Precedes Fusion of The Urethral Folds During Male Penile Urethral Development: The Double Zipper Hypothesis. The Journal of urology. 2014 Oct 3. PubMed PMID: 25286011.

Kurzrock E, Baskin L, Cunha G. Ontogeny of the Male Urethra: Theory of endodermal differentiation. Differentation. 1999;64:115-22.

Kurzrock E, Baskin L, Li Y, Cunha G. Epithelial-mesenchymal interactions in development of the mouse fetal genital tubercle. Cells Tissues and Organs. 1999;164:1015-20.


 




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