Si. Osada et Cve. Wright, Xenopus nodal-related signaling is essential for mesendodermal patterning during early embryogenesis, DEVELOPMENT, 126(14), 1999, pp. 3229-3240
Previously, we showed that Xenopus nodal-related factors (Xnrs) can act as
mesoderm inducers, and that activin induces Xnr transcription, suggesting t
hat Xnrs relay or maintain induction processes initiated by activin-like mo
lecules. We used a dominant negative cleavage mutant Xnr2 (cmXnr2) to carry
out loss-of-function experiments to explore the requirement for Xnr signal
ing in early amphibian embryogenesis, and the relationship between activin
and Xnrs. cmXnr2 blocked mesoderm induction caused by Xnr, but not activin,
RNA. In contrast, cmXnr2 did suppress mesoderm and endoderm induction by a
ctivin protein, while Xnr transcript induction was unaffected by cmXnr2, co
nsistent with an interference with the function of Xnr peptides that were i
nduced by activin protein treatment, The severe hyperdorsalization and gast
rulation defects caused by Xnr2 in whole embryos were rescued hy cmXnr2, es
tablishing a specific antagonistic relationship between the normal and clea
vage mutant proteins. Expression of cmXnr2 resulted in delayed dorsal lip f
ormation and a range of anterior truncations that were associated with dela
yed and suppressed expression of markers for dorsoanterior endoderm, in whi
ch the recently recognized head organizer activity resides. Reciprocally, X
nr2 induced dorsoanterior endodermal markers, such as cerberus. Xhex-1 and
Frzb, in animal cap ectoderm, The migratory behavior of head mesendoderm ex
planted from cmXnr2 RNA-injected embryos was drastically reduced, These res
ults indicate that Xnrs play crucial roles in initiating gastrulation, prob
ably by acting downstream of an activin-like signaling pathway that leads t
o dorsal mesendodermal specification, including setting up the head organiz
er.