Xnr5 and Xnr6 initiate embryonic induction

The dorsal lip region of the amphibian embryo was described as the organizer of body plan by Spemann and Mangold (1924). It was predicted that part of the mesoderm-inducing signal was released from the vegetal region beneath the mesoderm (Nieuwkoop, 1969). Following this work, the threesignal model was proposed, in which the first two kinds of signals are released from the vegetal region during the blastula stage (Slack et al., 1987). One is a pan or ventral mesoderm inducer, while the second induces dorsal mesoderm, including the Spemann’s organizer; the third signal is secreted from the organizer to dorsal-lateral mesoderm causing dorsalization. A number of dorsalizing factors have been identified previously, including noggin, chordin and follistatin, all of which inhibit BMP signaling by direct binding to BMP (Zimmerman et al., 1996; Piccolo et al., 1996; Fainsod et al., 1997). Several candidates for the first two signals have also been reported, and it has been suggested that a TGFβ signal is required in both mesoderm and endoderm induction (Asashima, 1994; Slack, 1994; Harland and Gerhart, 1997). Mutant analysis in other vertebrates, such as mouse and zebrafish, indicates that nodal-related genes belonging to the TGF-β superfamily mediate mesoderm induction signaling (Schier and Shen, 2000). Four nodal-related genes have been isolated in Xenopus . Xnr1, Xnr2 and Xnr4 have mesoderm induction activity (Jones et al., 1995; Lustig et al., 1996a; Joseph and Melton, 1997). Xnr3 is different from the other Xnr family members in that it does not have the conserved cysteine residue in its C-terminal region that is present in other TGFβ superfamily genes; it cannot induce mesoderm and has neural induction activity (Smith et al., 1995). Using the nodal-specific inhibitor cer-S, a recent report has shown that zygotic Xnrs act as both dorsal and ventral mesoderm inducers in vivo (Piccolo et al., 1999; Agius et al., 2000). Xnr1and Xnr2can also induce endodermal genes when they are expressed ectopically (prospective ectoderm; animal cap), and are involved in the determination of endodermal cell fate in the embryo by r gulating the expression of some genes (Kimelman and Griffin, 1998; Clements et al., 1999; Osada and Wright, 1999; Yasuo and Lemaire, 1999). In Xenopus , it was shown in embryos depleted of maternal mRNA using antisense oligodeoxynucleotides that VegTand βcateninare maternal determinants required for early embryonic events (Wylie et al., 1996; Zhang et al., 1998). The maternal transcripts of VegT, which encodes a transcription factor containing a T-box (Lustig et al., 1996b; Stennard et al., 1996; Zhang and King, 1996; Horb and Thomsen, 1997) are implicated in mesoderm induction by inducing Xnr1, Xnr2, Xnr4 and other TGFβ genes (Kofron et al., 1999). Kofron et al., showed that in VegT-depleted embryos the axis including head as well as trunk and tail, were completely rescued by Xnr1, Xnr2 and Xnr4. derrière also rescued the axis, but not the head. VegTis also required in endoderm determination, and 5319 Development 127, 5319-5329 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV3229