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First published online November 11, 2009
doi: 10.1242/10.1242/dev.039768

Development 136, 3959-3967 (2009)
Published by The Company of Biologists 2009
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Temporal and spatial dissection of Shh signaling in genital tubercle development

Congxing Lin1, Yan Yin1, G. Michael Veith1, Alexander V. Fisher1, Fanxin Long2,3 and Liang Ma1,3,*

1 Division of Dermatology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, MO 63110, USA
2 Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, MO 63110, USA
3 Department of Developmental Biology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, MO 63110, USA

* Author for correspondence (lima{at}dom.wustl.edu)

Accepted September 24, 2009

Genital tubercle (GT) initiation and outgrowth involve coordinated morphogenesis of surface ectoderm, cloacal mesoderm and hindgut endoderm. GT development appears to mirror that of the limb. Although Shh is essential for the development of both appendages, its role in GT development is much less clear than in the limb. Here, by removing Shh at different stages during GT development in mice, we demonstrate a continuous requirement for Shh in GT initiation and subsequent androgen-independent GT growth. Moreover, we investigated the Hh responsiveness of different tissue layers by removing or activating its signal transducer Smo with tissue-specific Cre lines, and established GT mesenchyme as the primary target tissue of Shh signaling. Lastly, we showed that Shh is required for the maintenance of the GT signaling center distal urethral epithelium (dUE). By restoring Wnt-Fgf8 signaling in Shh-/- cloacal endoderm genetically, we revealed that Shh relays its signal partly through the dUE, but regulates Hoxa13 and Hoxd13 expression independently of dUE signaling. Altogether, we propose that Shh plays a central role in GT development by simultaneously regulating patterning of the cloacal field and supporting an outgrowth signal.

Key words: Shh, Genital tubercle, Cloaca, Hox, Mouse


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