Biomedical subjects

S Y Sokol

Publications and source records attributed to S Y Sokol.

24 records · Page 2Linked to original sources

PubMed1995

Dorsalizing and neuralizing properties of Xdsh, a maternally expressed Xenopus homolog of dishevelled.

Signaling factors of the Wnt proto-oncogene family are implicated in dorsal axis formation during vertebrate development, but the molecular mechanism of this process is not known. Studies in Drosophila have indicated that the dishevelled gene product is required for wingless (Wnt1 homolog) signal transduction. We demonstrate that injection of mRNA encoding a Xenopus homolog of dishevelled (Xdsh) into prospective ventral mesodermal cells triggers a complete dorsal axis formation in Xenopus embryos. Lineage tracing experiments show that cells derived from the injected blastomere contribute to anterior and dorsal structures of the induced axis. In contrast to its effect on mesoderm, overexpression of Xdsh mRNA in prospective ectodermal cells triggers anterior neural tissue differentiation. These studies suggest that Wnt signal transduction pathway is conserved between Drosophila and vertebrates and point to a role for maternal Xdsh product in dorsal axis formation and in neural induction.

Adaptor Proteins, Signal Transducing↗

PubMed1994

The pregastrula establishment of gene expression pattern in Xenopus embryos: requirements for local cell interactions and for protein synthesis.

Although it has been proposed that mesoderm forms in the marginal zone of the amphibian embryo through inductive signaling from vegetal pole cells, the details of this process remain to be clarified. To determine when marginal zone cells become committed to mesodermal fates, cell contact and protein synthesis requirements for early transcriptional responses were analyzed in Xenopus blastulae. Marginal zone explants were isolated from embryos at different stages and either were cultured untreated, or were dissociated in a medium lacking calcium and magnesium ions, or cultured in the presence of cycloheximide. Whereas many mesoderm-specific transcripts are efficiently induced by activin in dissociated animal pole cells, the same markers were not activated in dissociated marginal zone cells, which were isolated from mid or even late blastulae and cultured in the absence of exogenous inducers. These observations suggest that early specification of mesodermal fates requires cell-cell interactions within the marginal zone and that the marginal zone cells are not committed to express early mesodermal markers until the late blastula stage. Specification of mesodermal fates was also assessed by the ability of marginal zone cells to express early mesodermal markers in the absence of protein synthesis. Induction of Xlim1, 1A11, and, partially, Xbrachyury transcripts in the marginal zone was blocked by cycloheximide treatment through late blastula stages, whereas Goosecoid and Xwnt8 mRNAs were expressed in the absence of protein synthesis, indicating that these sets of markers are activated in vivo through different pathways. These observations demonstrate that determination of mesoderm in the marginal zone is a multistep process which occurs during late blastula stages and depends on cell-cell contact and protein synthesis.

Animals↗

PubMed1994

Heparan sulfate proteoglycans are required for mesoderm formation in Xenopus embryos.

Mesoderm forms in the vertebrate embryo as a result of inductive interactions involving secreted growth factors and cell surface molecules. Proteoglycans have recently been implicated in the control of cell adhesion, migration and growth factor responsiveness. We have found that removal of glycosaminoglycan chains of proteoglycans from Xenopus ectodermal explants by heparinase, but not by chondroitinase, results in inhibition of elongation and mesodermal differentiation in response to signaling factors: activin, FGF and Wnt. Heparinase treatment differentially affected expression of early general and region-specific mesodermal markers, suggesting that mesodermal cell fates become specified in the early embryo via at least two signaling pathways which differ in their requirements for heparan sulfate proteoglycans. Addition of soluble heparan sulfate restored activin-mediated induction of muscle-specific actin gene in heparinase-treated explants. Finally, heparinase inhibited autonomous morphogenetic movements and mesodermal, but not neural, differentiation in dorsal marginal zone explants, which normally give rise to mesoderm in the embryo. These results directly demonstrate that heparan sulfate proteoglycans participate in gastrulation and mesoderm formation in the early embryo.

Activins↗

PubMed1993

Mesoderm formation in Xenopus ectodermal explants overexpressing Xwnt8: evidence for a cooperating signal reaching the animal pole by gastrulation.

It is demonstrated here that the ability of injected Xwnt8 RNA to trigger mesoderm formation in Xenopus presumptive ectoderm (animal caps) depends on the time of explantation. Animal caps isolated from Xwnt8 injected embryos at the late blastula/early gastrula stages differentiate mesodermal tissues whereas caps isolated from early blastula do not. This finding suggests that an endogenous signal reaches the animal cap by the late blastula stage and cooperates with Xwnt8 to induce mesoderm. Similarly, late animal caps isolated at st. 10 from lithium-treated embryos, but not those from control embryos, elongate and express muscle-specific actin transcripts. In addition, the data presented suggests that the cooperating signal is distributed homogeneously with respect to the future dorsoventral axis and may require FGF- and activin-dependent signal transduction pathways. These observations support a model in which mesoderm is induced in vivo by a combined action of several different signals.

Animals↗

PubMed1992

Interaction of Wnt and activin in dorsal mesoderm induction in Xenopus.

Both the activin and Wnt families of peptide growth factors are capable of inducing dorsal mesoderm in Xenopus embryos. Presumptive ventral ectoderm cells isolated from embryos injected with Xwnt8 mRNA were cultured in the presence of activin A to study the possible interactions between these two classes of signaling proteins. We find that overexpression of Xwnt8 RNA alters the response of ventral ectoderm to activin such that ventral explants differentiate dorsoanterior structures including notochord and eyes. This response is similar to the response of dorsal ectoderm to activin alone. When embryos are irradiated with uv light to inhibit dorsal axis formation, ectodermal explants differentiate notochord when they are induced by a combination of both signaling factors, but not when cells receive only one inducing signal (activin or Xwnt8). This result is further supported by the observation that goosecoid (gsc) mRNA, an early marker for dorsal mesoderm, is expressed in these explants only when they are injected with Xwnt8 mRNA followed by exposure to activin. Early morphogenetic movements of the induced cells and activation of muscle-specific actin and Brachyury (Xbra) genes also reveal a cooperation of activin A and Xwnt8 in mesoderm induction.

Actins↗

PubMed1987

Ir gene influence on DNP-specific B-memory-cell formation.

It is well known that Ir genes control the antibody production. To investigate whether they also influence B-memory-cell generation, CBA mice (nonresponders) were primed with dinitrophenyl-poly-(L-tyr,L-glu)-poly-(D,L-ala)-poly-(L-lys)-DNP-TGAL conjugate. At the same time animals were injected with ovalbumin (OVA) to activate OVA-specific T helpers. Two to four weeks later animals were challenged with DNP-OVA conjugate and the number of IgG-producing B cells was determined. The data presented indicate that carrier-specific MHC-restricted T helpers are not required for B-memory-cell generation. It is concluded that the defect of IgG response to DNP-TGAL in CBA mice is caused by a block in the maturation of memory cells to antibody-producing cells.

Animals↗