XBMPRII, A NOVEL XENOPUS TYPE-II RECEPTOR MEDIATING BMP SIGNALING IN EMBRYONIC-TISSUES

Bone Morphogenetic Proteins (BMPs) are potent regulators of embryonic cell fate that are presumed to initiate signal transduction in recipie nt cells through multimeric, transmembrane, serine/threonine kinase co mplexes made up of type I an,type II receptors, BMPRII was identified previously in mammals as the only type IT receptor that binds BMPs, bu t not activin or TGF beta, in vitro, We report the cloning and-functio nal analysis in vivo of its Xenopus homolog, XBMPRII, XBMPRII is expre ssed maternally and zygotically in an initially unrestricted manner, S trikingly, XBMPRII transcripts then become restricted to the mesoderma l-precursors during gastrulation, Expression is lower in the dorsal or ganizer region, potentially providing a mechanism to suppress the acti ons of BMP4 on dorsally fated tissues, Similar to the results seen for a truncated type I BMP receptor (tBR), a dominant-negative form of XB MPRII (tBRII) can dorsalize ventral mesoderm, induce extensive seconda ry body axes, block mesoderm induction by BMP4 and directly neuralize ectoderm, strongly suggesting that XBMPRII mediates BMP signals in viv o. However, although both tBRII and tBR can induce partial secondary a xes, marker analysis shows that tBRII-induced axes are more anteriorly extended, Additionally, coinjection of tBRII and tBR synergistically increases the incidence of secondary axis formation. A truncated activ in type II receptor (Delta XAR1) is known to block both activin and BM P signaling in vivo. Here we show that such crossreactivity does not o ccur for tBRII, in that it does not affect activin signaling, Furtherm ore, our studies indicate that the full-length activin type II recepto r (XAR1) overcomes a block in BMP4 signaling imposed by tBRII, implica ting XAR1 as a common component of BMP and activin signaling pathways in vivo, These data implicate XBMPRII as a type II receptor with high selectivity for BMP signaling, and therefore as a critical mediator of the effects of BMPs as mesodermal patterning agents and suppressors o f neural fate during embryogenesis.