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Molecular and Cellular Biology, May 2004, p. 4417-4427, Vol. 24, No. 10
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.10.4417-4427.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Transcription Factor RFX3 Directs Nodal Cilium Development and Left-Right Asymmetry Specification

E. Bonnafe,¹ M. Touka,¹ A. AitLounis,² D. Baas,^1, E. Barras,² C. Ucla,^2, A. Moreau,³ F. Flamant,⁴ R. Dubruille,¹ P. Couble,¹ J. Collignon,³ B. Durand,^1,* and W. Reith^2,">*

Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, Université Claude Bernard Lyon-1, F-69622 Villeurbanne,¹ Laboratoire de Biologie Moléculaire et Cellulaire, CNRS UMR 49, ENSL, F-69364 Lyon,⁴ Departement de Biologie du Développement, Institut Jacques-Monod, CNRS UMR, Université Paris 6-7, F-75251 Paris, France,³ Department of Pathology, University of Geneva Medical School, CMU, CH-1211 Geneva, Switzerland²

Received 8 September 2003/ Returned for modification 27 October 2003/ Accepted 6 February 2004

There are five members of the RFX family of transcription factors in mammals. While RFX5 plays a well-defined role in the immune system, the functions of RFX1 to RFX4 remain largely unknown. We have generated mice with a deletion of the Rfx3 gene. RFX3-deficient mice exhibit frequent left-right (LR) asymmetry defects leading to a high rate of embryonic lethality and situs inversus in surviving adults. In vertebrates, specification of the LR body axis is controlled by monocilia in the embryonic node, and defects in nodal cilia consequently result in abnormal LR patterning. Consistent with this, Rfx3 is expressed in ciliated cells of the node and RFX3-deficient mice exhibit a pronounced defect in nodal cilia. In contrast to the case for wild-type embryos, for which we document for the first time a twofold increase in the length of nodal cilia during development, the cilia are present but remain markedly stunted in mutant embryos. Finally, we show that RFX3 regulates the expression of D2lic, the mouse orthologue of a Caenorhabditis elegans gene that is implicated in intraflagellar transport, a process required for the assembly and maintenance of cilia. In conclusion, RFX3 is essential for the differentiation of nodal monocilia and hence for LR body axis determination.

Present address: IBCP, F-69367 Lyon, France.

Present address: Division of Medical Genetics, University of Geneva Medical School, CMU, CH-1211 Geneva, Switzerland.

B.D. and W.R. contributed equally to this work.

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