R-spondinとは何ものぞや？

spondinには比較的良く知られたThrombospondinに始まり、F-spondin諸々があるらしい。

1. Baenziger NL, Brodie GN, Majerus PW (January 1971). "A thrombin-sensitive protein of human platelet membranes". Proc. Natl. Acad. Sci. U.S.A. 68 (1): 240–3. ----これがthrombospondinの最初の報告のようだー1971年のことだ

R-spondinに限定してと文献検索をすると38報出てくる(as of July 6th, 2011)が、オリジナルは（おそらく）2004年の東京医科歯科大学からのものであろう。Rというのはroof plate-specific spondinから命名したと書いてある。

ーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーー
Biochim Biophys Acta. 2004 Jan 5;1676(1):51-62.

R-spondin, a novel gene with thrombospondin type 1 domain, was expressed in the dorsal neural tube and affected in Wnts mutants.

Kamata T, Katsube K, Michikawa M, Yamada M, Takada S, Mizusawa H.
Department of Neurology and Neurological Science, Graduate School of Tokyo Medical and Dental University, Japan.

• Abstract

• We identified a novel gene, which encodes a 265-amino-acid sequence with a thrombospondin (TSP) type 1 motif. Unlike the other secretory proteins of the TSP family, this gene encodes no apparent secretion cleavage site, but has a putative nuclear localization signal. Northern blot analysis showed transient expression in the central nervous system (CNS) during development. In situ hybridization showed its expression in the dorsal part of the neural tube on 10 and 12 dpc, especially in the boundary region between roof plate and neuroepithelium. This expression was enhanced in the rostral part. The signals were observed in other tissues such as truncal region neighboring forelimbs and mesenchymal tissues around the nasal cavity. We named this gene R-spondin (roof plate-specific spondin). Transfection of an epitope-tagged R-spondin into COS7 and 293 cells showed its localization in nuclei and medium, suggesting that R-spondin may become secretory or nuclear protein by some processing, while most of other proteins with TSP type 1 domain are secretory proteins. The expression of R-spondin was reduced in Wnt-1/3a double knockout mouse. R-spondin might be a novel marker of the boundary between the roof plate and neuroepithelium and may contribute to the development of dorsal neural tube under the regulation of Wnts.

ーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーー
この論文以降興味深い論文があるが、例えば・・・・・これ↓

Nat. Genet. 38, 1304–1309 (2006).

Parma, P. et al. R-spondin1 is essential in sex determination, skin differentiation and malignancy.

• R-spondins are a recently characterized small family of growth factors. Here we show that human R-spondin1 (RSPO1) is the gene disrupted in a recessive syndrome characterized by XX sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. Our data show, for the first time, that disruption of a single gene can lead to complete female-to-male sex reversal in the absence of the testis-determining gene, SRY.

SRYをさしおいて、潰すと性転換が起こる遺伝子としてR-spondin1が報告されている。