spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 17 July 2008
doi: 10.1242/dev.020586

Development 135, 2815-2825 (2008)
Published by The Company of Biologists 2008
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow All Versions of this Article:
dev.020586v1
135/16/2815    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Lin, C.
Right arrow Articles by Ma, L.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lin, C.
Right arrow Articles by Ma, L.

Tissue-specific requirements of β-catenin in external genitalia development

Congxing Lin1,4, Yan Yin1, Fanxin Long2,3 and Liang Ma1,2,*

1 Division of Dermatology, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
2 Department of Developmental Biology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
3 Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
4 Human Genetics Program, Tulane University School of Medicine, New Orleans, LA 70112, USA.

* Author for correspondence (e-mail: lima{at}dom.wustl.edu)

Accepted 13 June 2008

External genitalia are body appendages specialized for internal fertilization. Their development can be divided into two phases, an early androgen-independent phase and a late androgen-dependent sexual differentiation phase. In the early phase, the embryonic anlage of external genitalia, the genital tubercle (GT), is morphologically identical in both sexes. Although congenital external genitalia malformations represent the second most common birth defect in humans, the genetic pathways governing early external genitalia development and urethra formation are poorly understood. Proper development of the GT requires coordinated outgrowth of the mesodermally derived mesenchyme and extension of the endodermal urethra within an ectodermal epithelial capsule. Here, we demonstrate that β-catenin plays indispensable and distinct roles in each of the aforementioned three tissue layers in early androgen-independent GT development. WNT-β-catenin signaling is required in the endodermal urethra to activate and maintain Fgf8 expression and direct GT outgrowth, as well as to maintain homeostasis of the urethra. Moreover, β-catenin is required in the mesenchyme to promote cell proliferation. By contrast, β-catenin is required in the ectoderm to maintain tissue integrity, possibly through cell-cell adhesion during GT outgrowth. The fact that both endodermal and ectodermal β-catenin knockout animals develop severe hypospadias in both sexes raises the possibility that the deregulation of any of these functions can contribute to the etiology of congenital external genital defects in humans.

Key words: β-Catenin, Genitalia, Urethra, Fgf8, Hypospadias






© The Company of Biologists Ltd 2008