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H Steinbeisser

Publications and source records attributed to H Steinbeisser.

At least 37 records · Page 2Linked to original sources
PubMed1997

The dorsalizing and neural inducing gene follistatin is an antagonist of BMP-4.

Specific signaling molecules play a pivotal role in the induction and specification of tissues during early vertebrate embryogenesis. BMP-4 specifies ventral mesoderm differentiation and inhibits neural induction in Xenopus, whereas three molecules secreted from the organizer, noggin, follistatin and chordin dorsalize mesoderm and promote neural induction. Here we report that follistatin antagonizes the activities of BMP-4 in frog embryos and mouse teratocarcinoma cells. In Xenopus embryos follistatin blocks the ventralizing effect of BMP-4. In mouse P19 cells follistatin promotes neural differentiation. BMP-4 antagonizes the action of follistatin and prevents neural differentiation. In addition we show that the follistatin and BMP-4 proteins can interact directly in vitro. These data provide evidence that follistatin might play a role in modulating BMP-4 activity in vivo.

Animals↗
PubMed1997

Cortical rotation is required for the correct spatial expression of nr3, sia and gsc in Xenopus embryos.

Beta-catenin, a component of the wnt-signal-transduction pathway, is essential for the formation of the dorsal axis in Xenopus laevis embryos. On the dorsal side of the embryo, beta-catenin is translocated into the nuclei via a process linked to cortical rotation. When cortical rotation is blocked by UV-irradiation, nuclear beta-catenin is found in the vegetal pole of the embryo. Here we show that overexpression of beta-catenin in animal cap explants, in the absence of mesoderm induction, is sufficient to activate the expression of genes with dorsalizing activity such as siamois (sia) and nodal-related 3 (nr3) but not goosecoid (gsc). In embryos ventralized by UV-treatment, the expression of the dorsal-specific genes sia, nr3 and gsc is induced at the vegetal pole after the Mid-Blastula-Transition (MBT). While nr3 and sia expression continues in these embryos until gastrula stages, gsc transcription cannot be maintained. We propose that the spatial separation of the expression domains of genes with dorsalizing activities and the prospective mesodermal region results in the loss of dorsal structures in the embryo. The role of cortical rotation is to generate an overlap of the region with dorsal axis-forming activity, indicated by nuclear translocation of beta-catenin, and the prospective mesoderm in the marginal zone to assure the correct positioning of the Spemann organizer.

Animals↗
PubMed1996

Beta-catenin translocation into nuclei demarcates the dorsalizing centers in frog and fish embryos.

The question of how dorsal-ventral polarity is established in vertebrates is central to our understanding of their early development. Several lines of evidence suggest that wnt-signaling is involved in the induction of dorsal-specific gene expression in the Spemann Organizer of amphibians. Here, we show that beta-catenin, acting as a component of the wnt-pathway, transiently accumulates in nuclei on the dorsal side of Xenopus and zebrafish blastulae. The spatially restricted nuclear translocation of beta-catenin precedes the expression of dorsal-specific genes. In experimentally ventralized frog embryos the dorsal ventral pattern of beta-catenin nuclear staining is abolished; in contrast, embryos hyperdorsalized by Li-ions or by injection of Xwnt8 mRNA exhibit an enhanced nuclear accumulation of beta-catenin. The results show that translocation of beta-catenin into nuclei in the wake of wnt-signaling is an early step in the establishment of the dorsal-ventral axis in frog and fish embryos.

Animals↗
PubMed1995

The role of gsc and BMP-4 in dorsal-ventral patterning of the marginal zone in Xenopus: a loss-of-function study using antisense RNA.

The dorsal-specific homeobox gene goosecoid (gsc) and the bone morphogenetic protein 4 gene (BMP-4) are expressed in complementary regions of the Xenopus gastrula. Injection of gsc mRNA dorsalizes ventral mesodermal tissue and can induce axis formation in normal and UV-ventralized embryos. On the other hand, BMP-4 mRNA injection, which has a strong ventralizing effect on whole embryos, has been implicated in ventralization by UV, and can rescue tail structures in embryos dorsalized by LiCl. The above-mentioned putative roles for BMP-4 and gsc are based on gain-of-function experiments. In order to determine the in vivo role of these two genes in the patterning of the Xenopus mesoderm during gastrulation, partial loss-of-function experiments were performed using antisense RNA injections. Using marker genes that are expressed early in gastrulation, we show that antisense gsc RNA has a ventralizing effect on embryos, whereas antisense BMP-4 RNA dorsalizes mesodermal tissue. These loss-of-function studies also show a requirement for gsc and BMP-4 in the dorsalization induced by LiCl and in the ventralization generated by UV irradiation, respectively. Thus, both gain- and loss-of-function results for gsc and BMP-4 support the view that these two genes are necessary components of the dorsal and ventral patterning pathways in Xenopus embryos.

Animals↗
PubMed1995

Regulation of neural induction by the Chd and Bmp-4 antagonistic patterning signals in Xenopus.

In Drosophila the amount of neurogenic ectoderm, from which the central nervous system (CNS) derives, is regulated by a dorsal-ventral system of positional information in which two secreted molecules of antagonistic functions, decapentaplegic (dpp) and short-gastrulation (sog), play fundamental roles. The vertebrate homologue of dpp is either bmp-4 or bmp-2 (ref. 5), and the homologue os sog is chd (s-chordin). In Xenopus the CNS is induced by signals emanating from the organizer, and two proteins secreted by the organizer, noggin and follistatin, have been shown to induce neural tissue in animal-cap assays. Here we report that Chd, another organizer-specific secreted factor, has neuralizing activity and that this activity can be antagonized by Bmp-4. Inhibition of the function of the endogenous Bmp-4 present in the animal cap also leads to neural differentiation. We suggest that conserved molecular mechanisms involving chd/sog and bmp-4/dpp gene products pattern the ectoderm in Xenopus and in Drosophila.

Animals↗
PubMed1994

Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes.

A Xenopus gene whose expression can be activated by the organizer-specific homeobox genes goosecoid and Xnot2 was isolated by differential screening. The chordin gene encodes a novel protein of 941 amino acids that has a signal sequence and four Cys-rich domains. The expression of chordin starts in Spemann's organizer subsequent to that of goosecoid, and its induction by activin requires de novo protein synthesis. Microinjection of chordin mRNA induces twinned axes and can completely rescue axial development in ventralized embryos. This molecule is a potent dorsalizing factor that is expressed at the right time and in the right place to regulate cell-cell interactions in the organizing centers of head, trunk, and tail development.

Activins↗
PubMed1994

On the function of BMP-4 in patterning the marginal zone of the Xenopus embryo.

Bone morphogenetic protein 4 (BMP-4) is expressed in the ventral marginal zone of the gastrulating embryo. At late gastrula stage this gene is expressed in the ventral-most part of the slit blastopore and in tissues that derive from it. At tailbud stages BMP-4 is expressed in the spinal cord roof plate, neural crest, eye and auditory vesicle. The interactions of BMP-4 with dorsal genes such as goosecoid (gsc) and Xnot-2 were studied in vivo. In embryos ventralized by UV irradiation and suramin treatment, BMP-4 zygotic transcripts accumulate prematurely and the entire marginal zone expresses this gene. The patterning effect of BMP-4 on ventro-posterior development can be revealed by a sensitive assay involving the injection of BMP-4 mRNA in the ventral marginal zone of embryos partially dorsalized with LiCl, which leads to the complete rescue of trunk and tail structures. The experiments presented here argue that BMP-4 may act in vivo as a ventral signal for the proper patterning of the marginal zone, actively interacting with dorsal genes such as gsc and Xnot-2. A model is proposed in which the timing of expression of various marginal zone-specific genes plays a central role in patterning the mesoderm.

Animals↗
PubMed1994

Mesodermal patterning by a gradient of the vertebrate homeobox gene goosecoid.

Amphibian mesoderm arises from the marginal zone of the early gastrula and generates various tissues such as notochord, muscle, kidney, and blood. Small changes (twofold) in the amount of microinjected messenger RNA encoding the goosecoid (gsc) homeodomain protein resulted in marked changes in the differentiation of mesoderm in Xenopus laevis. At least three thresholds were observed, which were sufficient to specify four mesodermal cell states. Endogenous gsc messenger RNA was expressed in the marginal zone in a graded fashion that is congruent with a role for this gene in dorso-ventral patterning of mesoderm at the early gastrula stage.

Animals↗
PubMed1994

The evolution of vertebrate gastrulation.

The availability of molecular markers now permits the analysis of the common elements of vertebrate gastrulation. While gastrulation appears to be very diverse in the vertebrates, by analyzing a head-organizer marker, goosecoid, and a marker common to all forming mesoderm, Brachyury, we attempt to identify homologous structures and equivalent stages in Xenopus, zebrafish, chick and mouse gastrulation. Using a tail-organizer marker, Xnot-2, we also discuss how the late stages of gastrulation lead to the formation of the postanal tail, a structure characteristic of the chordates.

Animals↗
PubMed1993

Xenopus axis formation: induction of goosecoid by injected Xwnt-8 and activin mRNAs.

In this study, we compare the effects of three mRNAs-goosecoid, activin and Xwnt-8- that are able to induce partial or complete secondary axes when injected into Xenopus embryos. Xwnt-8 injection produces complete secondary axes including head structures whereas activin and goosecoid injection produce partial secondary axes at high frequency that lack head structures anterior to the auditory vesicle and often lack notochord. Xwnt-8 can activate goosecoid only in the deep marginal zone, i.e., in the region in which this organizer-specific homeobox gene is normally expressed on the dorsal side. Activin B mRNA, however, can turn on goosecoid in all regions of the embryo. We also tested the capacity of these gene products to restore axis formation in embryos in which the cortical rotation was blocked by UV irradiation. Whereas Xwnt-8 gives complete rescue of anterior structures, both goosecoid and activin give partial rescue. Rescued axes including hindbrain structures up to level of the auditory vesicle can be obtained at high frequency even in the absence of notochord structures. The possible functions of Wnt-like and activin-like signals and of the goosecoid homeobox gene, and their order of action in the formation of Spemann's organizer are discussed.

Activins↗
PubMed1993

Tail formation as a continuation of gastrulation: the multiple cell populations of the Xenopus tailbud derive from the late blastopore lip.

Three lines of evidence suggest that tail formation in Xenopus is a direct continuation of events initiated during gastrulation. First, the expression of two gene markers, Xbra and Xnot2, can be followed from the blastopore lip into distinct cell populations of the developing tailbud. Second, the tip of the tail retains Spemann's tail organizer activity until late stages of development. Third, lineage studies with the tracer DiI indicate that the cells of the late blastopore are fated to form specific tissues of the tailbud, and that intercalation of dorsal cells continues during tail elongation. In particular, the fate map shows that the tip of the tail is a direct descendant of the late dorsal blastopore lip. Thus, the tailbud is not an undifferentiated blastema as previously thought, but rather consists of distinct cell populations which arise during gastrulation.

Animals↗
PubMed1993

Xenopus goosecoid: a gene expressed in the prechordal plate that has dorsalizing activity.

gsc is a homeobox gene expressed in the dorsal lip of the blastopore in Xenopus. Its mRNA can mimic many aspects of Spemann's organizer activity when microinjected into the ventral side of the embryo. In the present study we analyze gsc expression in late gastrula and neurula embryos of Xenopus. At these stages gsc is expressed in the prechordal plate, an anterior mesodermal structure underlying the forebrain. Furthermore, we studied the dorsalizing activity of gsc in animal caps and found that UV-sensitive cofactors in the marginal zone are required to induce dorso-anterior mesoderm in concert with gsc. FGF, an inducer of ventral mesoderm, cannot substitute for these factors.

Animals↗
PubMed1992

Gastrulation in the mouse: the role of the homeobox gene goosecoid.

Mouse goosecoid is a homeobox gene expressed briefly during early gastrulation. Its mRNA accumulates as a patch on the side of the epiblast at the site where the primitive streak is first formed. goosecoid-expressing cells are then found at the anterior end of the developing primitive streak, and finally in the anteriormost mesoderm at the tip of the early mouse gastrula, a region that gives rise to the head process. Treatment of early mouse embryos with activin results in goosecoid mRNA accumulation in the entire epiblast, suggesting that a localized signal induces goosecoid expression during development. Transplantation experiments indicate that the tip of the murine early gastrula is the equivalent of the organizer of the amphibian gastrula.

Activins↗
PubMed1992

Ureotelism as the prevailing mode of nitrogen excretion in larvae of the marsupial frog Gastrotheca riobambae (Fowler) (Anura, Hylidae).

1. Embryos from the pouch of the marsupial hylid frog Gastrotheca riobambae excrete urea. 2. Free-living tadpoles of G. riobambae excrete mainly urea, in comparison with tadpoles of other hylid frogs. 3. The activity of arginase is high in embryos from the pouch, and in tadpoles of G. riobambae. 4. The ureotelism of G. riobambae larvae is an adaptation for prolonged incubation in the pouch of the mother, and for development in limited amounts of water.

Animals↗
PubMed1992

Goosecoid and the organizer.

The molecular nature of Spemann's organizer phenomenon has long attracted the attention of embryologists. goosecoid is a homeobox gene with a DNA-binding specificity similar to that of Drosophila bicoid. Xenopus goosecoid is expressed on the dorsal side of the embryo before the dorsal lip is formed. Cells expressing goosecoid are fated to become pharyngeal endoderm, head mesoderm and notochord. Transplantation of goosecoid mRNA to the ventral side of Xenopus embryos by microinjection mimics the properties of Spemann's organizer, leading to the formation of twinned body axes, goosecoid is activated by dorsal inducers and not affected by ventral inducers. In the mouse, goosecoid is expressed in the anterior tip of the primitive streak. The availability of two early markers, goosecoid and Brachyury, opens the way for the comparative analysis of the vertebrate gastrula. The results suggest that the goosecoid homeodomain protein is an integral component of the biochemical pathway leading to Spemman's organizer phenomenon.

Animals↗
PubMed1991

Molecular nature of Spemann's organizer: the role of the Xenopus homeobox gene goosecoid.

This study analyzes the function of the homeobox gene goosecoid in Xenopus development. First, we find that goosecoid mRNA distribution closely mimics the expected localization of organizer tissue in normal embryos as well as in those treated with LiCl and UV light. Second, goosecoid mRNA accumulation is induced by activin, even in the absence of protein synthesis. It is not affected by bFGF and is repressed by retinoic acid. Lastly, microinjection of goosecoid mRNA into the ventral side of Xenopus embryos, where goosecoid is normally absent, leads to the formation of an additional complete body axis, including head structures and abundant notochordal tissue. The results suggest that the goosecoid homeodomain protein plays a central role in executing Spemann's organizer phenomenon.

Activins↗