Hoxa2 downregulates Six2 in the neural crest-derived mesenchyme.
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.
Kutejova
Eva
E
Department of Developmental Biology, Max-Planck Institute of Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany.
Engist
Bettina
B
Mallo
Moisés
M
Kanzler
Benoît
B
Bobola
Nicoletta
N
D000818:Animals; D001483:Base Sequence; D001934:Branchial Region / Q000196:embryology / Q000378:metabolism; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D006257:Head / Q000196:embryology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009432:Neural Crest / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D018398:Homeodomain Proteins; C489833:Hoxa2 protein, mouse; D012333:RNA, Messenger; C497420:Six2 protein, mouse; D014157:Transcription Factors