Tsukushi--A New BMP Antagonist

Science's STKE  21 Sep 2004:
Vol. 2004, Issue 251, pp. tw339
DOI: 10.1126/stke.2512004tw339

During chick embryonic development, the formation of the primitive streak and of Hensen's node (which regulates axis formation, mesoderm dorsalization, and induction of the nervous system) depends on the inhibition of bone morphogenetic protein (BMP) signaling. Ohta et al. screened a chick lens library and identified chick-Tsukushi (C-TSK), which encoded a secreted protein that belongs to the small leucine-rich proteoglycan (SLRP) family. C-TSK was expressed in the chick primitive streak and in Hensen's node. C-TSK mRNA injected into Xenopus embryos could induce formation of a secondary dorsal axis; in Xenopus embryo explants, it promoted mesoderm dorsalization and the expression of neural markers. When coinjected into Xenopus embryos, C-TSK and BMP mRNAs antagonized each other's effects; however, C-TSK could not antagonize the effects of a constitutively active BMP receptor, which suggests that it acted upstream of BMP receptor activation. Coimmunoprecipitation analysis indicated that C-TSK formed a ternary complex with BMP, and the BMP antagonist chordin and coinjection studies indicated that C-TSK and chordin cooperated in suppressing BMP activity. COS-7 cells expressing TSK transplanted into chick embryos together with the middle primitive streak or together with cells expressing cVg1 and Wnt1 were able to induce ectopic node formation, whereas C-TSK siRNA inhibited node induction. Thus, TSK appears to act cooperatively with chordin to inhibit BMP and promote the induction of Hensen's node.

K. Ohta, G. Lupo, S. Kuriyama, R. Keynes, C. E. Holt, W. A. Harris, H. Tanaka, S.-i. Ohnuma, Tsukushi functions as an organizer inducer by inhibition of BMP activity in cooperation with chordin. Dev. Cell 7, 347-358 (2004). [Online Journal]