![]() It has characteristic features of most TGFβ family members ( Kingsley, 1994): a hydrophobic signal sequence at the amino terminus, a pro region, and a mature C-terminal region containing seven cysteines that are involved in dimerization, secretion and receptor-binding. The nodalrelated gene we have cloned is identical to the Xnr1 gene described by Jones et al. (1995) identified a third Xenopus nodal-related gene, Xnr3 (a.k.a. (1995) identified two Xenopus nodal-related genes, Xnr1 and Xnr2, and Smith et al. While this work was underway, reports of three Xenopus nodalrelated genes have been published. When we began to characterize the clone, sequence comparisons indicated that it was a member of the TGFβ superfamily of secreted proteins, and was most closely related to nodal, a gene required for mesoderm induction in the mouse ( Zhou et al., 1993). Sequence analysis revealed that the 1.6 kb clone has an open reading frame of 406 amino acids encoding a protein with a predicted molecular mass of 46 kDa. Thus Xnr1 may act together with noggin to induce axial pattern during gastrulation and may also be involved later in the establishment of left-right asymmetry. ![]() Although Xnr1 has mesoderm-and neural-inducing activity on its own, in conjunction with noggin it can mimic three other activities of the gastrula organizer including the induction of a complete secondary axis, the formation of notochord and the stimulation of tissue movements reminiscent of convergent extension behavior. To examine the function of Xnr1 during gastrulation, we have expressed it alone or in conjunction with the secreted protein noggin. In our study we found that Xnr1 is also strongly expressed in two regions of the post-gastrula embryo: in two small stripes of cells flanking the posterior notochord in late neurula stage embryos and in dorsolateral mesoderm restricted to the left side of tailbud stage embryos. It was reported that Xnr1 is only strongly expressed during late blastula and gastrula stages of development, with enrichment in the organizer. (1995) described the homology-based cloning of a Xenopus nodal-related gene, designated Xnr1, that is identical to the gene we have cloned. While this work was underway, Jones et al. ![]() We have used this assay to identify and functionally characterize a gene related to nodal, a secreted TGFβ family member required for mesoderm formation in the mouse ( Conlon et al., 1994 Zhou et al., 1993). We have recently developed a paracrine assay that can be used to identify genes capable of acting in a non-cell-autonomous manner to respecify presumptive ectoderm ( Lustig and Kirschner, 1995). ![]() Neuralization of Xenopus ectodermal explants is also induced by follistatin ( Hemmati-Brivanlou et al., 1994), an activin antagonist originally isolated based upon its ability to inhibit follicle-stimulating hormone release from the pituitary ( Nakamura et al., 1990). Both noggin and chordin neuralize animal pole explants (presumptive ectoderm) that would otherwise form epidermal tissue. Chordin was identified by combining subtractive cDNA hybridization with in situ RNA hybridization to identify genes highly expressed in the Xenopus organizer ( Sasai et al., 1994). Noggin was isolated in a functional screen for genes capable of rescuing dorsal axis development in ventralized Xenopus embryos ( Smith and Harland, 1992). When this work was begun, only three secreted proteins had been shown to be specifically expressed in the organizer during gastrulation: noggin ( Smith and Harland, 1992), chordin ( Sasai et al., 1994) and follistatin ( Hemmati-Brivanlou et al., 1994). Although the biological functions of the organizer have been intensively studied for over seventy years, only in the last five years have candidate secreted molecules that carry out these functions been identified.
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