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First published online 5 January 2005
doi: 10.1242/dev.01536

Development 132, 469-478 (2005)
Published by The Company of Biologists 2005
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Hoxa2 downregulates Six2 in the neural crest-derived mesenchyme

Eva Kutejova1, Bettina Engist1, Moisés Mallo2, Benoît Kanzler1 and Nicoletta Bobola1,*

1 Department of Developmental Biology, Max-Planck Institute of Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany
2 Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal

* Author for correspondence (e-mail: bobola{at}immunbio.mpg.de)

Accepted 16 November 2004

The Hoxa2 transcription factor acts during development of the second branchial arch. As for most of the developmental processes controlled by Hox proteins, the mechanism by which Hoxa2 regulates the morphology of second branchial arch derivatives is unclear. We show that Six2, another transcription factor, is genetically downstream of Hoxa2. High levels of Six2 are observed in the Hoxa2 loss-of-function mutant. By using a transgenic approach to overexpress Six2 in the embryonic area controlled by Hoxa2, we observed a phenotype that is reminiscent of the Hoxa2 mutant phenotype. Furthermore, we demonstrate that Hoxa2 regulation of Six2 is confined to a 0.9 kb fragment of the Six2 promoter and that Hoxa2 binds to this promoter region. These results strongly suggest that Six2 is a direct target of Hoxa2.

Key words: Hoxa2, Six2, Hox genes, Branchial arches, Neural crest, Mouse




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