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First published online June 8, 2005
doi: 10.1242/10.1242/dev.01885

Development 132, 3055-3067 (2005)
Published by The Company of Biologists 2005
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Comparative analysis of genes downstream of the Hoxd cluster in developing digits and external genitalia

John Cobb and Denis Duboule*

National Research Center (NCCR) `Frontiers in Genetics', Department of Zoology and Animal Biology, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland

* Author for correspondence (e-mail: denis.duboule{at}zoo.unige.ch)

Accepted 29 April 2005

Mammalian Hox genes encode transcription factors that are crucial for proper morphogenesis along the various body axes. Despite their extensive structural and functional characterization, the nature of their target genes remains elusive. We have addressed this question by using DNA microarrays to screen for genes whose expression in developing distal forelimbs and genital eminences was significantly modified in the absence of the full Hoxd gene complement. This comparative approach not only identified specific candidate genes, but also allowed the examination of whether a similar Hox expression pattern in distinct tissues leads to the modulation of the same or different downstream genes. We report here a set of potential target genes, most of which were not previously known to play a role in the early stages of either limb or genital bud development. Interestingly, we find that the majority of these candidate genes are differentially expressed in both structures, although often at different times. This supports the idea that both appendices involve similar genetic controls, both upstream and downstream of the Hox gene family. These results highlight the surprising mechanistic relationship between these rather different body parts and suggest a common developmental strategy to build up the most distal appendicular structures of the body, i.e. the digits and the penis/clitoris.

Key words: Hox genes, Development, Penis, Clitoris, Sgk, Epha3, Mouse




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