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Development, Vol 124, Issue 20 3929-3941, Copyright © 1997 by Company of Biologists
JOURNAL ARTICLES |
C Kimura, N Takeda, M Suzuki, M Oshimura, S Aizawa and I Matsuo
Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Honjo, Japan.
Previous studies suggested that the Otx2 gene plays an essential role in the development of cranial skeletons and nerves of mesencephalic neural crest origin. To clarify this role, we have identified the cis-acting elements in mouse and pufferfish Otx2 genes responsible for the expression in the crest cells using a transgenic approach with the lacZ reporter gene. In mouse, 49 bp sequences in the proximal 5' region upstream were essential and sufficient to direct the transgene expression in the cephalic mesenchyme. In pufferfish, the 1.1 kb distal region, located far downstream (from +14.4 to +15.5 kb), had almost identical activity. Between them, several DNA sequences were conserved, and mutational analyses indicated that motif A was critical for the transgene expression in the premandibular region while motif B was critical in both premandibular and mandibular regions. Motif B, CTAATTA, contains the core motif for binding of homeodomain proteins while motif A, TAAATCTG, does not match any known consensus binding sequences for transcriptional factors. The cephalic mesenchyme that expressed beta-galactosidase under these cis-elements is most likely to correspond to mesencephalic crest cells. Thus the molecular machinery regulating Otx2 expression in these cells appears to be conserved between mouse and fish, implying a crucial role of the Otx2 gene in development of the neural-crest-derived structures of the gnathostome rostral head.
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