Competence modifiers synergize with growth factors during mesoderm induction and patterning in xenopus

Abstract

Embryological concepts refined over decades are being reinvestigated with the goal of defining these in terms of specific biochemical signaling pathways. Studies in the amphibian Xenopus laevis have established that specific members of the fibroblast growth factor (FGF) and transforming growth factor f3 (TGFb) families are involved in mesoderm induction, though theobserved spatial distribution of dorsal and ventral mesoderm cannot readily be explained by the reported specificity and localization of these signaling agents or their receptors (reviewed by Kimelman et al., 1992). As highlighted below, localized competence modifiers may regulate the responsiveness of cells to more widespread mesoderm-inducing agents. Thus, cellular competence to respond to signals, a principle recognized earlier this century, may play a significant role in modulating the position and type of mesoderm that is formed in the embryo. Signaling Centers in Mesoderm Induction and Patterning Mesoderm induction in Xenopus is part of a series of spatially localized signaling events that also establish the body axes during development. Embryological analyses of these signaling centers have established the spatial and temporal pattern of information involved in mesoderm induction and patterning (Gerhart et al., 1991). Initially, a postfertilization rotation of the cortical region of the egg activates cytoplasmic dorsal determinants on the side opposite the sperm entry point (Figure 1, curved arrow). Treatments that block this rotation, such as ultraviolet irradiation of the vegetal hemisphere, block dorsal development and result in an embryo of predominantly ventral character. Transplantation of cells from dorsal regions of nonirradiated hosts rescues normal dorsal axial structures in irradiated embryos, demonstrating that these cells contain dorsal determinants. The dorsal region of cytoplasm, which is activated by the cortical rotation and subdivided into the cells capable of rescuing ultraviolet-irradiated embryos, constitutes the early blastulaorganizer (or Nieuwkoop center, NC; stippled area in pre-midblastula [pre-MBT] embryo, Figure 1). Based on a related cell transplantation assay, by the 32-cell stage, the activity of dorsal determinants is highest in the equatorial and vegetal dorsal blastomeres and extends into the dorsal blastomeres of the animal hemisphere (Kageura, 1990; references in Kimelman et al., 1992). Our depiction of the Nieuwkoop center (Figure 1) is drawn to accommodate these data. Embryological data indicate that, prior to the midblastula stage, this Nieuwkoop center signals equatorial cells to become dorsal mesoderm. Equatorial cells that do not receive this early dorsaldetermining activity either contain or will receive from vegetal cells signals that induce them to become ventral mesoderm. The induced dorsal mesoderm of the equatorial region, perhaps via an intermediary late blastula organizer (Gerhart et al., 1991) will form the gastrula (Spemann’s) organizer (Figure 1, 0 in post-MST embryo), whose cells are fated to give rise to notochord and head mesoderm. The activities of the gastrula organizer include the initiation of the morphogenetic movementsof gastrulation, the patterning of lateral mesoderm, and the induction of neural tissue. Thus, it is thought that, by late blastula stage, cells enter pathways leading to differentiation as either dorsal (hatching in post-MBT embryo) or ventral (dark stippling) mesoderm. During gastrulation and after the initiation of zygotic transcription, progression along these pathways is altered by dorsalizing signals (arrow in post-MBT embryo), so that intermediate types of mesoderm (light stippling in late gastrula embryo) are formed, in addition to dorsal and ventral mesoderm (hatching and dark stippling, respectively, in late gastrula embryo). How well can these sequential signaling events be explained in biochemical terms? Candidate signaling agents and their receptors have been identified that may participate in manystepsof mesoderm induction and patterning, but the sequential organizing centers discussed above have not been defined biochemically in terms of the discrete localization or activities of factors. With regard to the Nieuwkoop center, two types of secreted proteins, some members of the Wnt family (re-