Endogenous Msx1 antisense transcript: in vivo and in vitro evidences, structure, and potential involvement in skeleton development in mammals.

Blin-Wakkach C; Lezot F; Ghoul-Mazgar SHotton DMonteiro STeillaud CPibouin LOrestes-Cardoso SPapagerakis PMacdougall MRobert BBerdal A

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Endogenous Msx1 antisense transcript: in vivo and in vitro evidences, structure, and potential involvement in skeleton development in mammals.

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摘要

Msx1 is a key factor for the development of tooth and craniofacial skeleton and has been proposed to play a pivotal role in terminal cell differentiation. In this paper, we demonstrated the presence of an endogenous Msx1 antisense RNA (Msx1-AS RNA) in mice, rats, and humans. In situ analysis revealed that this RNA is expressed only in differentiated dental and bone cells with an inverse correlation with Msx1 protein. These in vivo data and overexpression of Msx1 sense and AS RNA in an odontoblastic cell line (MO6-G3) showed that the balance between the levels of the two Msx1 RNAs is related to the expression of Msx1 protein. To analyze the impact of this balance in the Msx-Dlx homeoprotein pathway, we analyzed the effect of Msx1, Msx2, and Dlx5 overexpression on proteins involved in skeletal differentiation. We showed that the Msx1-AS RNA is involved in crosstalk between the Msx-Dlx pathways because its expression was abolished by Dlx5. Msx1 was shown to down-regulate a master gene of skeletal cells differentiation, Cbfa1. All these data strongly suggest that the ratio between Msx1 sense and antisense RNAs is a very important factor in the control of skeletal terminal differentiation. Finally, the initiation site for Msx1-AS RNA transcription was located by primer extension in both mouse and human in an identical region, including a consensus TATA box, suggesting an evolutionary conservation of the AS RNA-mediated regulation of Msx1 gene expression.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2001年第13期|7336-7341|共6页
作者
Blin-Wakkach C; Lezot F; Ghoul-Mazgar SHotton DMonteiro STeillaud CPibouin LOrestes-Cardoso SPapagerakis PMacdougall MRobert BBerdal A;
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作者单位

Laboratory of Biology-Odontology, Institut National de la Sante et de la Recherche Medicale, E 0110, Institut des Cordeliers, IFR 58, 75006 Paris, France. biol_odonto_fr;

o.state.ct.us;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Gene Expression Regulation; Developmental; Homeodomain Proteins; Osteogenesis; 基因表达调控; 发育期; 同源域蛋白质类; 骨生成; RNA; 反义; 转录; 遗传;

Endogenous Msx1 antisense transcript: in vivo and in vitro evidences, structure, and potential involvement in skeleton development in mammals.

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