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First published online 17 October 2007
doi: 10.1242/dev.010991

Development 134, 3967-3973 (2007)
Published by The Company of Biologists 2007
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Research Report

Hox gene function in vertebrate gut morphogenesis: the case of the caecum

Giovanna Zacchetti1, Denis Duboule1,2,* and Jozsef Zakany1

1 National Research Centre `Frontiers in Genetics', Department of Zoology and Animal Biology, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
2 School of Life Sciences, Ecole Polytechnique Fédérale, Lausanne, Switzerland.

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

Accepted 23 August 2007

SUMMARY

The digestive tract is made of different subdivisions with various functions. During embryonic development, the developing intestine expresses combinations of Hox genes along its anterior to posterior axis, suggesting a role for these genes in this regionalization process. In particular, the transition from small to large intestine is labelled by the transcription of all Hoxd genes except Hoxd12 and Hoxd13, the latter two genes being transcribed only near the anus. Here, we describe two lines of mice that express Hoxd12 ectopically within this morphological transition. As a consequence, budding of the caecum is impeded, leading to complete agenesis in homozygous individuals. This effect is concurrent with a dramatic reduction of both Fgf10 and Pitx1 expression. Furthermore, the interactions between `anterior' Hox genes and ectopic Hoxd12 suggest a model whereby anterior and posterior Hox products compete in controlling Fgf10 signalling, which is required for the growth of this organ in mice. These results illuminate components of the genetic cascade necessary for the emergence of this gut segment, crucial for many vertebrates.

Key words: Hox target genes, Budding morphogenesis, Genetic analysis, Gut regionalization, Mouse organogenesis






© The Company of Biologists Ltd 2007