A highly conserved enhancer in the Dlx5/Dlx6 intergenic region is the site of cross-regulatory interactions between Dlx genes in the embryonic forebrain

被引:275
作者
Zerucha, T
Stühmer, T
Hatch, G
Park, BK
Long, QM
Yu, GY
Gambarotta, A
Schultz, JR
Rubenstein, JLR
Ekker, M
机构
[1] Ottawa Hosp, Loeb Hlth Res Inst, Ottawa, ON K1Y 4E9, Canada
[2] Univ Ottawa, Dept Med, Ottawa, ON K1Y 4E9, Canada
[3] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1Y 4E9, Canada
[4] Univ Calif San Francisco, Nina Ireland Lab Dev Neurobiol, Ctr Neurobiol & Psychiat, Dept Psychiat, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Program Neurosci, San Francisco, CA 94143 USA
[6] Univ Calif San Francisco, Program Dev Biol, San Francisco, CA 94143 USA
[7] Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA
[8] Tularik Inc, S San Francisco, CA 94080 USA
关键词
diencephalon; evolution; homeobox; mouse; striatum; telencephalon; zebrafish;
D O I
10.1523/JNEUROSCI.20-02-00709.2000
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Four Dlx homeobox genes, Dlx1, Dlx2, Dlx5, and Dlx6 are expressed in the same primordia of the mouse forebrain with temporally overlapping patterns. The four genes are organized as two tail-to-tail pairs, Dlx1/Dlx2 and Dlx5/Dlx6, a genomic arrangement conserved in distantly related vertebrates like zebrafish. The Dlx5/Dlx6 intergenic region contains two sequences of a few hundred base pairs, remarkably well conserved between mouse and zebrafish. Reporter transgenes containing these two sequences are expressed in the forebrain of transgenic mice and zebrafish with patterns highly similar to endogenous Dlx5 and Dlx6 expression. The activity of the transgene is drastically reduced in mouse mutants lacking both Dlx1 and Dlx2, consistent with the decrease in endogenous Dlx5 and Dlx6 expression. These results suggest that cross-regulation by Dlx proteins, mediated by the intergenic sequences, is essential for Dlx5 and Dlx6 expression in the forebrain. This hypothesis is supported by cotransfection and DNA-protein binding experiments. We propose that the Dlx genes are part of a highly conserved developmental pathway that regulates forebrain development.
引用
收藏
页码:709 / 721
页数:13
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