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At least 433 records · Page 24Linked to original sources
PubMed2000

Left-right asymmetry in BMP4 signalling pathway during chick gastrulation.

Determination of the left-right (L-R) axis was shown recently to implicate several genes, among which TGFbeta-related molecules such as Activin betaB, lefty1 and 2 and Nodal. We show here that Bmp4 and its signal transduction pathway partners BMPR IA and Smad1 are transiently expressed on the right side of Hensen's node, when L-R polarity is being established. Moreover, Smad1 is expressed asymmetrically in the nascent notochord. These observations suggest a role for a BMP4-dependent autocrine or paracrine mechanism during early L-R determination.

Amino Acid Sequence↗
PubMed2000

The Toll/IL-1 receptor binding protein MyD88 is required for Xenopus axis formation.

The Toll/Dorsal pathway regulates dorsoventral axis formation in the Drosophila embryo. We had previously obtained evidence that a homologous pathway exists in Xenopus, however, its role during normal frog development had not been established. Here we report the cloning of Xenopus MyD88 (XMyD88), whose mammalian homologs are adaptor proteins linking Toll/IL-1 receptors and IRAK kinases. We show that in the frog embryo overexpression of a dominant-negative form of XMyD88 blocked Toll receptor activity, specifically inhibited axis formation and reduced expression of pivotal organizer genes. The observed stage-dependency of interference suggests a function for maternal XMyD88 soon after fertilization. We conclude that XMyD88 activity is required for normal Spemann organizer formation, implying an essential role for maternal Toll/IL-1 receptors in Xenopus axis formation.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Expression of ADAMTS1 during murine development.

ADAMTS1/METH1 belongs to the ADAMTS (a disintegrin and metalloprotease with thrombospondin repeats) family of proteins that currently comprises 18 members. Targeted inactivation of the ADAMTS1 gene results in morphological defects in the kidney, adrenal gland, and adipose tissue in addition to growth retardation and infertility in females. To gain further insight on the biology of ADAMTS1, we examined its expression pattern in the developing mouse from embryonic day 10 (E10) to E18. Expression analysis by RNase protection assays revealed detectable levels of ADAMTS1 transcripts in E10-E18 yolk sac, placenta, brain, heart, lung, limb bud, liver, spleen, and kidney, with much lower levels in the adult. Using in situ hybridization, we have localized ADAMTS1 transcripts predominantly to the epithelium of the developing lung, pancreas, kidney and to a subset of neurons in a temporally restricted manner. Expression was also detected in the tunica media of the aorta, pulmonary, and hepatic vessels.

ADAM Proteins↗
PubMed1998

Nested expression and sequential downregulation of the Xenopus caudal genes along the anterior-posterior axis.

Expression of the Xenopus Xcad-1 and Xcad-2 genes initiates during early gastrulation exhibiting a dorsoventral asymmetry in their domains of transcription. At mid-gastrulation the ventral preference becomes stronger and the caudal genes take up a posterior localization in their expression, which they will maintain until their downregulation along the dorsal midline. Comparison of the three Xenopus caudal genes revealed a temporal and spatial nested set of expression patterns. The transcription of the caudal genes is sequentially downregulated with the one expressed most caudally (Xcad-2) being shut down first, this sequence is most evident along the dorsal midline. This pattern of expression suggests a role for the caudal genes as posterior determinants along the anteroposterior axis. In chicken, mouse, man and Xenopus three members of the caudal family have been identified in the genome. Even though in Xenopus the Xcad-3 gene has been previously described, in order to obtain a better insight on the role of the caudal genes a comparative study of all three frog genes was performed.

Animals↗
PubMed1998

Conserved Spätzle/Toll signaling in dorsoventral patterning of Xenopus embryos.

The Spätzle/Toll signaling pathway controls ventral axis formation in Drosophila by generating a gradient of nuclear Dorsal protein. Dorsal controls the downstream regulators dpp and sog, whose patterning functions are conserved between insects and vertebrates. Although there is no experimental evidence that the upstream events are conserved as well, we set out to ask if a vertebrate embryo can respond to maternal components of the fly Dorsal pathway. Here we demonstrate a dorsalizing activity for the heterologous Easter, Spätzle and Toll proteins in UV-ventralized Xenopus embryos, which is inhibited by a co-injected dominant Cactus variant. We conclude that the Dorsal signaling pathway is a component of the conserved dorsoventral (d/v) patterning system in bilateria.

Animals↗
PubMed1998

BMP-2/-4 and Wnt-8 cooperatively pattern the Xenopus mesoderm.

Establishment of the dorsoventral axis is central to animal embryonic organization. In Xenopus two different classes of signaling molecules function in the dorsoventral patterning of the mesoderm. Both the TGF-beta-related products of the BMP-2 and BMP-4 genes and the Wnt molecule encoded by Xenopus Wnt-8 specify ventral fate and appear to inhibit dorsal mesodermal development. The similar functions of these molecularly very different classes of signaling molecules prompted us to study their mutual regulation and to closely compare their roles in mesoderm patterning. We find that Wnt-8 and BMP-4 are indistinguishable in their abilities to induce expression of ventral genes. Although BMP-2/-4 signaling regulates Wnt-8 expression, these genes do not function in a linear pathway because Wnt-8 overexpression cannot compensate for an inhibition of BMP-2/-4 function, but rather BMP-4 overexpression rescues ventral gene expression in embryos with inhibited Wnt-8 function. We further find that Wnt-8 and BMP-2/-4 differ in their abilities to regulate dorsal gene expression. While BMP-4 appears to generally inhibit the expression of dorsal genes, XenopusWnt-8 only inhibits the expression of the notochord marker Xnot. Whereas the inhibitory effect of BMP-2/-4 localizes dorsal mesodermal fate, our results suggest that Xenopus Wnt-8 functions in the further patterning of the dorsal mesoderm into the most dorsal sector from which the notochord develops and the dorsolateral sector from where the somites differentiate.

Animals↗
PubMed1998

A POU protein regulates mesodermal competence to FGF in Xenopus.

XLPOU91, a POU-homeobox gene is expressed in a narrow window during early Xenopus development. We show that ectopic expression of XLPOU91 RNA causes severe posterior truncations in embryos without inhibiting the formation of Spemann's organizer. Ectopic XLPOU91 expression also inhibits mesoderm induction by fibroblast growth factor (FGF) and activin in animal cap explants. Using antisense RNA, we depleted endogenous XLPOU91 protein in animal caps. Gastrula-stage animal caps expressing XLPOU91 antisense RNA do not lose competence to FGF, unlike controls, these animal caps express XBra after FGF treatment. Endogenous XLPOU91 levels are peaking when FGF mesoderm-inducing competence is lost in animal caps. Thus XLPOU91 protein may act as a competence switch during early development, as XLPOU91 levels increase in the embryo, the mesoderm response to FGF is lost.

Animals↗
PubMed2000

Pattern formation and regulation of gene expressions in chick recombinant limbs.

Recombinant limbs were performed by ensembling dissociated-reaggregated wing bud mesoderm inside an ectodermal hull. The zone of polarizing activity was excluded from the mesoderm used to perform the recombinant limbs (non-polarized recombinants), and grafted when desired (polarized recombinants). Reorganization of patterning progressively occurred in the newly formed progress zone under the influence of the apical ectodermal ridge (AER), explaining the proximo-distal gradient of morphogenesis observed in developed recombinant limbs. The AER, without the influence of the polarizing region (ZPA), was sufficient to direct outgrowth and appropriate proximo-distal patterning, as observed in the expression of the Hoxa-11 and Hoxa-13 genes. The development of the recombinant limbs coursed with symmetric AER and downregulation of Bmp expression in the mesoderm supporting a negative effect of Bmp signaling upon the apical ridge. The recombinant ectoderm maintained previously established compartments of gene expressions and organized a correct dorso-ventral patterning in the recombinant progress zone. Finally, the ZPA effect was only detected on Bmp expression and pattern formation along the antero-posterior axis.

Animals↗
PubMed2000

Surface ectoderm is necessary for the morphogenesis of somites.

The paraxial mesoderm of the neck and trunk of mouse embryos undergoes extensive morphogenesis in forming somites. Paraxial mesoderm is divided into segments, it elongates along its anterior posterior axis, and its cells organize into epithelia. Experiments were performed to determine if these processes are autonomous to the mesoderm that gives rise to the somites. Presomitic mesoderm at the tailbud stage was cultured in the presence and absence of its adjacent tissues. Somite segmentation occurred in the absence of neural tube, notochord, gut and surface ectoderm, and occurred in posterior fragments in the absence of anterior presomitic mesoderm. Mesodermal expression of Dll1 and Notch1, genes with roles in segmentation, was largely independent of other tissues, consistent with autonomous segmentation. However, surface ectoderm was found to be necessary for elongation of the mesoderm along the anterior-posterior axis and for somite epithelialization. To determine if there is specificity in the interaction between ectoderm and mesoderm, ectoderm from different sources was recombined with presomitic mesoderm. Surface ectoderm from only certain parts of the embryo supported somite epithelialization and elongation. Somite epithelialization induced by ectoderm was correlated with expression of the basic-helix-loop-helix gene Paraxis in the mesoderm. This is consistent with the genetically defined requirement for Paraxis in somite epithelialization. However, trunk ectoderm was able to induce somite epithelialization in the absence of strong Paraxis expression. We conclude that somitogenesis consists of autonomous segmentation patterned by Notch signaling and nonautonomous induction of elongation and epithelialization by surface ectoderm.

Animals↗
PubMed2000

Regulatory gene expression patterns reveal transverse and longitudinal subdivisions of the embryonic zebrafish forebrain.

To shed light on the organization of the rostral embryonic brain of a lower vertebrate, we have directly compared the expression patterns of dlx, fgf, hh, hlx, otx, pax, POU, winged helix and wnt gene family members in the fore- and midbrain of the zebrafish. We show that the analyzed genes are expressed in distinct transverse and longitudinal domains and share expression boundaries at stereotypic positions within the fore- and midbrain. Some of these shared expression boundaries coincide with morphological landmarks like the pathways of primary axon tracts. We identified a series of eight transverse diencephalic domains suggestive of neuromeric subdivisions within the rostral brain. In addition, we identified four molecularly distinct longitudinal subdivisions and provide evidence for a strong bending of the longitudinal rostral brain axis at the cephalic flexure. Our data suggest a strong conservation of early forebrain organization between lower and higher vertebrates.

Animals↗
PubMed2001

From fertilization to gastrulation: axis formation in the mouse embryo.

Although much remains unknown about how the embryonic axis is laid down in the mouse, it is now clear that reciprocal interactions between the extraembryonic and embryonic lineages establish and reinforce patterning of the embryo. At early post-implantation stages, the extraembryonic ectoderm appears to impart proximal-posterior identity to the adjacent proximal epiblast, whereas the distal visceral endoderm signals to the underlying epiblast to restrict posterior identity as it moves anteriorward. At gastrulation, the visceral endoderm is necessary for specifying anterior primitive streak derivatives, which, in turn, pattern the anterior epiblast. Polarity of these extraembryonic tissues can be traced back to the blastocyst stage, where asymmetry has been linked to the point of sperm entry at fertilization.

Animals↗
PubMed2001

Axis formation and patterning in zebrafish.

A large collection of mutations affecting zebrafish embryogenesis was described in 1996. The cloning of the affected genes has now provided novel insights into the role and regulation of signaling by BMP, Nodal, Wnt, FGF, Hedgehog, Delta, Slit, retinoic acid and lipids. Detailed analyses have revealed a complex genetic network that patterns the early embryo.

Animals↗
PubMed1996

RNA localization and the development of asymmetry during Drosophila oogenesis.

Recent work on axis formation in Drosophila has revealed that polarity arises in several distinct stages during oogenesis. One cell of a germline cyst is selected to become the oocyte, the position of the oocyte determines the posterior of the follicle, and the position of the oocyte nucleus determines the dorsal side. Each of these symmetry-breaking steps involves the asymmetric localization of a unique structure, leading to polarization of the cytoskeleton and the localization of specific mRNAs.

Animals↗
PubMed2000

Left-right development: the roles of nodal cilia.

Cilia on the ventral side of the mouse node have been implicated in initiating the left-right axis during embryonic development, but how cilia relate to other factors in the left-right pathway and the mechanism by which cilia convey patterning information remain uncertain.

Animals↗
PubMed1996

Early developmental expression and experimental axis determination by the chicken Vg1 gene.

BACKGROUND: Genes of the transforming growth factor beta (TGF beta) superfamily have been implicated in the earliest steps of developmental patterning in vertebrates. In Xenopus, the Vg1 gene is a candidate for the initiator of axis formation: its RNA and protein are broadly but appropriately localized at the start of development, and processed Vg1 protein is a powerful inducer of organized axial tissue in blastular animal caps in vitro and when locally produced in vivo after injection of Vg1 mRNA into blastomeres. Site-specific proteolytic processing occurs ubiquitously for most TGF beta members, producing the active peptide ligand, but is tightly restricted, by unknown mechanisms, for endogenous Vg protein in Xenopus and zebrafish embryos. This restriction may be involved in the spatial localization of activity required for an organizing role. RESULTS: We have characterized an amniote (chick) orthologue of Vg1, cVg1, and examined its developmental expression. The early expression of cVg1 includes a phase broadly related to the known time and site of axis (primitive streak) initiation; the initial transcription of cVg1 is centred in the posterior marginal zone (PMZ), a region of the blastoderm known to contain the axial organizing activity at this stage. We also observed later neural and paraxial mesodermal expression of cVg1, which has not been described previously for Vg homologues in other vertebrates. We have grafted transfected COS cells, producing processed cVg1 protein, to peripheral positions around the chick early blastoderm. Such grafts initiate formation of morphologically complete primitive streaks, simulating the properties of grafts from the PMZ. CONCLUSIONS: In vertebrate development, Vg genes may be required for an evolutionarily conserved early step in positioning or induction of the axis.

Amino Acid Sequence↗
PubMed1998

Axis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and beta-catenin.

Signaling by the Wnt family of extracellular proteins is critical in a variety of developmental processes in which cell and tissue polarity are established [1-5]. Wnt signal transduction has been studied mostly by the genetic approach in Drosophila and Caenorhabditis elegans [1,2,5], but the biochemical mechanisms involved remain to be elucidated. The Wnt pathway also operates during axis determination in vertebrates [3,5]. Frizzled receptors transduce a signal to Dishevelled, leading to inactivation of glycogen synthase kinase 3 (GSK3) and regulation of gene expression by the complex of beta-catenin with LEF/TCF (lymphocyte enhancer factor/T-cell factor) transcription factors [3,5]. Axin is a negative regulator of Wnt signaling and dorsal axial development in vertebrates [6]. Here, we demonstrate that axin is associated with GSK3 in the Xenopus embryo and we localize the GSK3-binding domain to a short region of axin. Binding of GSK3 correlates with the ability of axin to inhibit axial development and with the axis-inducing activity of its dominant-negative form (delta RGS). We also find that wild-type axin, but not delta RGS, forms a complex with beta-catenin. Thus, axin may act as a docking station mediating negative regulation of beta-catenin by GSK3 during dorsoventral axis determination in vertebrate embryos.

Animals↗
PubMed2003

Cerebellar infarction secondary to os odontoideum.

A 43-year-old man developed cerebellar infarction due to atlantoaxial dislocation associated with os odontoideum. Cervical X-ray films confirmed os odontoideum, and conventional angiography revealed irregular narrowing of the right vertebral artery at the axis level. A correlation between the vertebral artery lesion and atlantoaxial instability was shown with 3-dimensional (3-D) computed tomographic (CT) angiography. This is the first case of atlantoaxial dislocation with vertebral artery stenosis demonstrated 3-D CT angiography. 3-D CT angiography can support the conventional angiography with respect to the diagnosis and management of vertebral artery insufficiency associated with occipitocervical deformity.

Adult↗