Sonic hedgehog signaling from the urethral epithelium controls external genital development

  • Perriton C
  • Powles N
  • Chiang C
 et al. 
  • 51


    Mendeley users who have this article in their library.
  • 165


    Citations of this article.


External genital development begins with formation of paired genital swellings, which develop into the genital tubercle. Proximodistal outgrowth and axial patterning of the genital tubercle are coordinated to give rise to the penis or clitoris. The genital tubercle consists of lateral plate mesoderm, surface ectoderm, and endodermal urethral epithelium derived from the urogenital sinus. We have investigated the molecular control of external genital development in the mouse embryo. Previous work has shown that the genital tubercle has polarizing activity, but the precise location of this activity within the tubercle is unknown. We reasoned that if the tubercle itself is patterned by a specialized signaling region, then polarizing activity may be restricted to a subset of cells. Transplantation of urethral epithelium, but not genital mesenchyme, to chick limbs results in mirror-image duplication of the digits. Moreover, when grafted to chick limbs, the urethral plate orchestrates morphogenetic movements normally associated with external genital development. Signaling activity is therefore restricted to urethral plate cells. Before and during normal genital tubercle outgrowth, urethral plate epithelium expresses Sonic hedgehog (Shh). In mice with a targeted deletion of Shh, external genitalia are absent. Genital swellings are initiated, but outgrowth is not maintained. In the absence of Shh signaling, Fgf8, Bmp2, Bmp4, Fgf10, and Wnt5a are downregulated, and apoptosis is enhanced in the genitalia. These results identify the urethral epithelium as a signaling center of the genital tubercle, and demonstrate that Shh from the urethral epithelium is required for outgrowth, patterning, and cell survival in the developing external genitalia. © 2002 Elsevier Science (USA).

Author-supplied keywords

  • Apoptosis
  • External genitalia
  • Hox gene
  • Mouse embryo
  • Polarizing activity
  • Sonic hedgehog
  • Urethra

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Claire L. Perriton

  • Nicola Powles

  • Chin Chiang

  • Mark K. Maconochie

  • Martin J. Cohn

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free