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J. Biol. Chem., Vol. 282, Issue 21, 15843-15850, May 25, 2007

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Brorin, a Novel Secreted Bone Morphogenetic Protein Antagonist, Promotes Neurogenesis in Mouse Neural Precursor Cells^*

From the Department of Genetic Biochemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Sakyo, Kyoto 606-8501, Japan

We identified a gene encoding a novel secreted protein in mice and humans and named it Brorin. Mouse Brorin consists of 324 amino acids with a putative secreted signal sequence at its amino terminus and two cysteine-rich domains in its core region. Positions of 10 cysteine residues in the domains of Brorin are similar to those in the cysteine-rich domains of members of the Chordin family. However, the amino acid sequence of Brorin is not significantly similar to that of any other member of the Chordin family, indicating that Brorin is a unique member of the family. Mouse Brorin protein produced in cultured cells was efficiently secreted into the culture medium. The protein inhibited the activity of bone morphogenetic protein 2 (BMP2) and BMP6 in mouse preosteoblastic MC3T3-E1 cells. Mouse Brorin was predominantly expressed in neural tissues in embryos and also predominantly expressed in the adult brain. In the brain, the expression was detected in neurons, but not glial cells. The neural tissue-specific expression profile of Brorin is quite distinct from that of any other member of the Chordin family. Brorin protein promoted neurogenesis, but not astrogenesis, in mouse neural precursor cells. The present findings indicate that Brorin is a novel secreted BMP antagonist that potentially plays roles in neural development and functions.

Received for publication, February 22, 2007 , and in revised form, March 30, 2007.

^* This work was supported by a grant-in-aid for Scientific Research from the Ministry of Education, Science, Culture, and Sports of Japan (to N. I.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Genetic Biochemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Yoshida-Shimoadachi, Sakyo, Kyoto 606-8501, Japan. Tel.: 81-75-753-4540; Fax: 81-75-753-4600; E-mail: itohnobu{at}pharm.kyoto-u.ac.jp.

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