The zebrafish-secreted matrix protein you/Scube2 is implicated in long-range regulation of Hedgehog signaling

被引：99

作者：

Kawakami, A

Nojima, Y

Toyoda, A

Takahoko, M

Satoh, M

Tanaka, H

Wada, H

Masai, I

Terasaki, H

Sakaki, Y

Takeda, H

Okamoto, H

机构：

[1] Univ Tokyo, Dept Biol Sci, Bunkyo Ku, Tokyo 1130033, Japan

[2] RIKEN, Brain Sci Inst, Lab Dev Gene Regulat, Wako, Saitama 3510198, Japan

[3] RIKEN, Sequence Technol Team, Genome Core Technol Facil, Genom Sci Ctr,Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[4] Japan Sci & Technol Corp, Core Res Evolut Sci & Technol, Chuo Ku, Tokyo 1030027, Japan

来源：

CURRENT BIOLOGY | 2005年 / 15卷 / 05期

关键词：

D O I：

10.1016/j.cub.2005.02.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The Hedgehog (Hh) signal plays a pivotal role in induction of ventral neuronal and muscle cell types around the midline during vertebrate development [1]. We report that the gene disrupted in zebrafish you mutants, in which Hh signaling is impaired, encodes the secreted matrix protein Scube2. Consistently, epistasis analyses suggested that Scube2 functions upstream of Hh ligands or through a parallel pathway. In addition, overexpression analyses suggested that Scube2 is an essential, but a permissive, mediator of Hh signaling in zebrafish embryos. Surprisingly, the you gene is expressed in the dorsal neural tube, raising the possibility that Scube2 could indirectly act via a long-range regulator of Hh signaling. The dorsal Bmps have a long-range and opposing influence on Hh signaling [2-5]. We show that neural plate patterning is affected in you mutants in a way that is consistent with the aberrant long-range action of a Bmp-dependent signal. We further show that Bmp activity can be attenuated by the coexpression of Scube2. Our data support the idea that Scube2 can modulate the long-range action of Bmp-dependent signaling in the neural tube and somites.

引用

页码：480 / 488

页数：9

共 35 条

[21]

Yang R.B., Ng C.K., Wasserman S.M., Colman S.D., Shenoy S., Mehraban F., Komuves L.G., Tomlinson J.E., Topper J.N., Identification of a novel family of cell-surface proteins expressed in human vascular endothelium, J. Biol. Chem., 277, pp. 46364-46373, (2002)

[22]

Grimmond S., Larder R., Van Hateren N., Siggers P., Morse S., Hacker T., Arkell R., Greenfield A., Expression of a novel mammalian epidermal growth factor-related gene during mouse neural development, Mech. Dev., 102, pp. 209-211, (2001)

[23]

Wu B.T., Su Y.H., Tsai M.T., Wasserman S.M., Topper J.N., Yang R.B., A novel secreted, cell-surface glycoprotein containing multiple epidermal growth factor-like repeats and one CUB domain is highly expressed in primary osteoblasts and bones, J. Biol. Chem., 279, pp. 37485-37490, (2004)

[24]

Lee K.J., Jessell T.M., The specification of dorsal cell fates in the vertebrate central nervous system, Annu. Rev. Neurosci., 22, pp. 261-294, (1999)

[25]

Liem Jr. K.F., Tremml G., Jessell T.M., A role for the roof plate and its resident TGFβ-related proteins in neuronal patterning in the dorsal spinal cord, Cell, 91, pp. 127-138, (1997)

[26]

Du S.J., Devoto S.H., Westerfield M., Moon R.T., Positive and negative regulation of muscle cell identity by members of the hedgehog and TGF-b gene families, J. Cell Biol., 139, pp. 145-156, (1997)

[27]

Rissi M., Wittbrodt J., Delot E., Naegeli M., Rosa F.M., Zebrafish Radar: A new member of the TGF-beta superfamily defines dorsal regions of the neural plate and the embryonic retina, Mech. Dev., 49, pp. 223-234, (1995)

[28]

Sidi S., Goutel C., Peyrieras N., Rosa F.M., Maternal induction of ventral fate by zebrafish radar, Proc. Natl. Acad. Sci. USA, 100, pp. 3315-3320, (2003)

[29]

Barth K.A., Kishimoto Y., Rohr K.B., Seydler C., Schulte-Merker S., Willson S.W., Bmp activity establishes a gradient of positional information throughout the entire neural plate, Development, 126, pp. 4977-4987, (1999)

[30]

Kishimoto Y., Lee K.-H., Zon L., Hammerschmidt M., Schulte-Merker S., The molecular nature of zebrafish swirl: BMP2 function is essential during early dorsoventral patterning, Development, 124, pp. 4457-4466, (1997)

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