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H J Yost

Publications and source records attributed to H J Yost.

At least 19 recordsLinked to original sources
PubMed1998

The left-right coordinator: the role of Vg1 in organizing left-right axis formation.

The asymmetries of internal organs are consistently oriented along the left-right axis in all vertebrates, and perturbations of left-right orientation lead to significant congenital disease. We propose a model in which a "left-right coordinator" interacts with the Spemann organizer to coordinate the evolutionarily conserved three-dimensional asymmetries in the embryo. The Vg1 cell-signaling pathway plays a central role in left-right coordinator function. Antagonists of Vg1 alter left-right development; antagonists of other members of the TGFbeta family do not. Cell-lineage directed expression of Vg1 protein can fully invert the left-right axis (situs inversus), can randomize left-right asymmetries, or can "rescue" a perturbed left-right axis in conjoined twins to normal orientation (situs solitus), indicating that Vg1 can mimic left-right coordinator activity. These are the first molecular manipulations in any vertebrate by which the left-right axis can be reliably controlled.

Activins↗
PubMed1998

Left-right development from embryos to brains.

Bilateran animals have external bilateral symmetry along the dorsoventral (DV) and anteroposterior (AP) axes. Internal left-right asymmetries appear to be consistently aligned along the left-right (LR) axis with respect to the other axes. Left-right development is most apparent in the directional looping of the cardiac tube, the coiling and placement of the intestines, the positioning of internal organs such as liver, gallbladder, pancreas, and stomach. In addition, there are obvious morphological asymmetries in the brains of some vertebrates and functional left-right asymmetries in the activities of the brain, as assessed by psychological testing, MRI, and the analysis of lesions. There are several fundamental questions: What are the origins of the left-right axis, and are they highly conserved across metazoans? Once the left-right axis is established by the initial breaking of bilateral symmetry, what is the genetic pathway that perpetrates left-right development? What are the cellular and tissue mechanics that lead to morphogenesis during, for example, the looping of the cardiac tube, the coiling of the gut, or asymmetric brain development? Finally, do the asymmetric developmental pathways of each organ system take register from the same initial event that establishes the left-right axis, or are there separate mechanisms that orient heart, gut, and brain left-right asymmetry with respect to the DV and AP axes? These questions are beginning to be experimentally addressed, and papers in this issue of Developmental Genetics make contributions to several aspects in the burgeoning field of left-right development. Recent reviews have summarized the emerging genes and pathways in vertebrate left-right development [Wood, 1997; Harvey, 1998; Ramsdell and Yost, 1998]. Here, I give an overview of the contributions in this issue to the fundamental questions in left-right development.

Animals↗
PubMed1998

Maintenance of asymmetric nodal expression in Xenopus laevis.

Vertebrate species display consistent left-right asymmetry in the arrangement of their internal organs. This asymmetry reflects the establishment of the left-right axis and the alignment of the organs along this axis during development. Members of the TGF-beta family of molecules have been implicated in both the establishment and signaling of left-right axis information. Asymmetric expression of one member, nodal (called Xnr-1 in the frog, Xenopus laevis), is highly conserved among species. The nodal-related genes are normally expressed in the left lateral plate mesoderm prior to the development of morphologic asymmetry. Expression patterns of nodal have been correlated with heart situs in mouse, chick, and frog and our previous work has implicated the dorsal midline structures in the regulation of nodal expression and cardiac laterality. In this study, three approaches were used to address the embryologic and molecular basis of asymmetric Xnr-1 expression. First, notochord and lateral plate recombinants were performed and showed that notochord can repress Xnr-1 expression in lateral plate mesoderm explants derived from either the left or the right side. Second, lateral plate mesoderm grafts indicated that Xnr-1 expression is specified but not determined at neurula stages and can subsequently be repatterned. These experiments suggest that a repressive signal from the notochord is required for maintenance of asymmetric Xnr-1 expression and that Xnr-1 expression is regulated by signals outside of the lateral plate mesoderm. Third, candidate molecules were injected to test for their ability to alter Xnr-1 expression pattern in the lateral plate. Late injection of activin protein on the right side of the embryo induced ectopic Xnr-1 expression and randomized cardiac orientation. This suggests that activin or a related TGF-beta molecule is involved in the proximal regulation of asymmetric Xnr-1 expression.

Activins↗
PubMed1998

Left-right development in Xenopus and zebrafish.

One of the most striking features of the vertebrate body plan is that most exterior structures are bilaterally symmetric while many interior structures are left-right asymmetric. Left-right asymmetries are displayed in the heart, the circulatory, digestive and respiratory systems and in the central nervous system. A fundamental question in the study of all patterning events, including left-right axis formation, is how does asymmetry arise from apparent symmetry. A second important question that is perhaps unique to the study of left-right development, is how does the left-right axis align with the asymmetries that develop along the orthogonal axes; dorsal-ventral and anterior-posterior. Recent experiments in Xenopus laevis and zebrafish address both of these questions and have identified signaling molecules and interactions with midline cells that regulate left-right development.

Animals↗
PubMed1998

Molecular mechanisms of vertebrate left-right development.

Patterning of all tissues and organs in the vertebrate embryo occurs along the dorsoventral (DV), anteroposterior (AP), and left-right (LR) body axes. Whereas significant progress has been made in identifying the processes underlying DV and AP patterning, relatively little is known about mechanisms guiding LR development. The significant incidence of human disease conditions associated with LR laterality defects, particularly those of the cardiovascular system, underscores the importance of understanding how LR asymmetries become established in the embryo. The focus of this review is on recently identified genes that are involved in generation of vertebrate LR asymmetry, and the proposed cellular and molecular mechanisms by which they might function in initiation, propagation and interpretation of LR patterning information.

Animals↗
PubMed1998

The genetics of midline and cardiac laterality defects.

Left-right asymmetric looping of the cardiac tube during embryogenesis places the segments of the cardiac tube that give rise to the left and right chambers into their appropriate spatial orientation. Cardiac looping is required for subsequent formation of septa, valves, and outflow tract. Defects in embryonic left-right axis formation represent a significant portion of congenital heart malformations. Recent discoveries make it apparent that the orientation of cardiac tube looping is dependent on a cascade of genes in noncardiac embryonic cells, including lateral cells and midline cells, before neural tube closure. These observations suggest a linkage between complex cardiac defects and subtle midline defects in early embryos.

Animals↗
PubMed1997

Left-right asymmetry of a nodal-related gene is regulated by dorsoanterior midline structures during Xenopus development.

Development of asymmetry along the left-right axis is a critical step in the formation of the vertebrate body plan. Disruptions of normal left-right patterning are associated with abnormalities of multiple organ systems, including significant congenital heart disease. The mouse nodal gene, and its homologues in chick and Xenopus, are among the first genes known to be asymmetrically expressed along the left-right axis before the development of organ asymmetry. Alterations in the expression pattern of mouse nodal and the chick homologue (cNR-1) have been associated with defects in the development of left-right asymmetry and cardiac looping (Levin, M., Johnson, R. L., Stern, C. D., Kuehn, M. and Tabin, C. (1995) Cell 82, 803-814; Collignon, J., Varlet, I. and Robertson, E. J. (1996) Nature 381, 155-158; Lowe, L. A., Supp, D. M., Sampath, K., Yokoyama, T., Wright, C. V. E., Potter, S. S., Overbeek, P. and Kuehn, M. R. (1996) Nature 381, 158-161). Here, we show that the normal expression patterns of the Xenopus nodal-related gene (Xnr-1) are variable in a large population of embryos and that Xnr-1 expression is altered by treatments that perturb normal left-right development. The incidence of abnormal Xnr-1 expression patterns correlates well with cardiac reversal rates in both control and experimentally treated Xenopus embryos. Furthermore, dorsal midline structures, including notochord and/or hypochord and neural floorplate, regulate Xnr-1 expression prior to the specification of cardiac left-right orientation by repression of Xnr-1 expression in the right lateral plate mesoderm during closure of the neural tube. The correlation of Xnr-1 expression and orientation of cardiac looping suggests that Xnr-1 is a component of the left-right signaling pathway required for the specification of cardiac orientation in Xenopus, and that dorsal midline structures normally act to repress the signaling pathway on the right side of the embryo.

Animals↗
PubMed1996

Initiation of vertebrate left-right axis formation by maternal Vg1.

In the development of the three-dimensional vertebrate body plan, the left-right axis is linked to the dorsoventral and anterioposterior axes. In humans, altered left-right development results in severe cardiovascular and visceral abnormalities in individuals and in conjoined twins. Although zygotically transcribed genes that are asymmetrically expressed have been identified, the mechanism by which left-right asymmetries are established during embryogenesis is unknown. Here we show that the Xenopus maternal gene Vg1, a member of the TGF-beta family of cell-signalling molecules which are implicated in dorsoanterior development, initiates left-right axis formation. Altered expression of Vg1 on the right side of 16-cell embryos or disruption of endogenous Vg1 signalling on the left side randomizes cardiac and visceral left-right orientation and alters expression of Xnr-1, a nodal-related molecular marker for left-right development. Furthermore, the orientation of the left-right axis in conjoined twins is dependent upon which cell-signalling molecule initiated twin formation and on whether the secondary axis is on the left or right side of the primary embryonic axis, implicating a molecular pathway leading to the formation of conjoined twins.

Activin Receptors↗
PubMed1996

Role of notochord in specification of cardiac left-right orientation in zebrafish and Xenopus.

The left-right body axis is coordinately aligned with the orthogonal dorsoventral and anterioposterior body axes. The developmental mechanisms that regulate axis coordination are unknown. Here it is shown that the cardiac left-right orientation in zebrafish (Danio rerio) is randomized in notochord-defective no tail and floating head mutants. no tail (Brachyury) and floating head (Xnot) encode putative transcription factors that are expressed in the organizer and notochord, structures which regulate dorsoventral and anterioposterior development in vertebrate embryos. Results from dorsal tissue extirpation and cardiac primordia explantation indicate that cardiac left-right orientation is dependent on dorsoanterior structures including the notochord and is specified during neural fold stages in Xenopus laevis. Thus, the notochord coordinates the development of all three body axes in the vertebrate body plan.

Animals↗
PubMed1996

Xenopus poly (A) binding protein maternal RNA is localized during oogenesis and associated with large complexes in blastula.

Maternal mRNAs are synthesized during oogenesis and often stored for use during early embryogenesis, before the onset of zygotic transcription. The temporal and spatial regulation of maternal RNAs is likely to be crucial mechanism for the establishment of the body pattern. In the course of a study that identified a Xenopus maternal mRNA that is translationally regulated along the dorsoventral axis, several RNAs were found to behave anomalously in polysomal analysis and are further characterized here. As controls for polysome analysis, elF4E RNA and D7.1 RNA were equally translated in both dorsal and ventral cells, whereas the cell-cell signaling factor noggin RNA was not translated in either cell type. Maternal RNAs encoding poly (A) binding protein (PABP), Vg1 and Xcat-2 were associated with large complexes that, in contrast to polysomes, were not dissociated in magnesium-free buffer. Vg1 and Xcat-2 maternal mRNAs have been shown to be localized during oogenesis to the vegetal hemisphere of the oocyte [Rebagliati et al., 1985; Mosquera et al., 1993]. In situ hybridization analysis indicated that PABP RNA was also localized during oogenesis, to the animal hemisphere in stage VI oocytes. This suggests that association of maternal mRNAs with large EDTA-insensitive mRNP complexes is correlated with intracellular localization, but the specific localization within the oocyte is dependent upon the RNA species.

Animals↗
PubMed1996

Embryonic expression patterns of Xenopus syndecans.

Syndecans are a family of heparan sulfate proteoglycans implicated in cell-cell and cell-matrix interactions. To investigate the roles of syndecans in early development, we identified three syndecan family members in Xenopus laevis: Xsyn-1, Xsyn-2, and Xsyn-3. Xsyn-1 and Xsyn-2 are maternal mRNAs localized to the animal pole in blastulae, and are expressed in the ectoderm of gastrulae. In neurulae, Xsyn-1 is restricted to non-neural ectoderm and Xsyn-2 is restricted to neural ectoderm. In tailbud embryos, the three syndecans are expressed in adjacent, non-overlapping patterns. Xsyn-2 is expressed in the heart while Xsyn-1 is expressed in the underlying anterior endoderm. Xsyn-3 is expressed in the hindbrain, midbrain, and forebrain, while Xsyn-2 is expressed in the intervening regions. These results suggest that different members of the syndecan family have distinct developmental roles, perhaps acting as barriers to define tissue boundaries.

Amino Acid Sequence↗
PubMed1996

The genetics of left-right development and heterotaxia.

Looping of the primitive heart tube is one of the earliest and most crucial steps in cardiac morphogenesis. Cardiac looping is dependent on normal left-right development, and defects in left-right development result in both heterotaxia and complex congenital heart disease. Single gene defects result in the wide spectrum of heterotaxy phenotypes, and conversely, different gene defects result in similar heterotaxy phenotypes. Elucidation of the molecular-genetic mechanisms of left-right development will greatly increase our understanding of the etiology of this complex group of congenital heart defects.

Animals↗
PubMed1995

Relocation of mitochondria to the prospective dorsal marginal zone during Xenopus embryogenesis.

Dorsal-ventral axis formation in Xenopus laevis begins with a cytoplasmic rotation during the first cell cycle and culminates in a series of cell interactions and movements during gastrulation and neurulation that lead to the formation of dorsal-anterior structures. Evidence reported here indicates that mitochondria are differentially redistributed along the prospective dorsal-ventral axis as a consequence of the cortical-cytoplasmic rotation during the first cell cycle. This finding reinvigorates a possibility that has been considered for many years: asymmetries in cytoplasmic components and metabolic activities contribute to the development of morphological asymmetries.

Animals↗
PubMed1995

Plasticity in the synthesis and storage of substance P and calcitonin gene-related peptide in primary afferent neurons during peripheral inflammation.

Several indices of peptidergic, primary afferent neural transmission in rat at the level of the lumbar spinal cord exhibited differential changes over time in response to adjuvant-induced inflammation of the hindpaw. The indices were measurements of the production of messenger RNA encoding the precursors for substance P and calcitonin gene-related peptide in dorsal root ganglia, the storage of substance P and calcitonin gene-related peptide in the dorsal spinal cord and the release of the peptides evoked by application of capsaicin to the dorsal spinal cord. A 47% decrease in the content of immunoreactive substance P in the dorsal half of the lumbar spinal cord, as determined by radioimmunoassay, was measured at 6 h following the injection of complete Freund's adjuvant into the hindpaw. Decreased content of immunoreactive SP persisted for four days, but was no longer present at eight days after the adjuvant injection. The content of immunoreactive calcitonin gene-related peptide in the dorsal spinal cord was decreased by 29% at one day following the injection of adjuvant into the rat hindpaw and 43% at two days; the content then increased to a level greater than that of control animals at eight days. The amount of messenger RNA encoding preprotachykinin and prepro-calcitonin gene-related peptide in L4-L6 dorsal root ganglia was determined from northern blot analysis of the total messenger RNA extracted from the dorsal root ganglia. Each species of messenger RNA had increased compared to the control animals at two days following the injection of adjuvant into the rat hindpaws and remained elevated after eight days. Thus, an increase in the messenger RNAs encoding substance P and calcitonin gene-related peptide in the dorsal root ganglia preceeded the recovery of the content of the peptides in the spinal cord. Morphometric studies of calcitonin gene-related peptide-immunoreactive perikarya in the L4 dorsal root ganglia indicated that the increase in messenger RNA occurred in neurons of the size that normally express calcitonin gene-related protein. Radioimmunoassay of the superfusate of the dorsal half of the lumbar spinal cord was used to measure the release of immunoreactive substance P and immunoreactive calcitonin gene-related protein in vitro. Although the basal release of immunoreactive substance P and immunoreactive calcitonin-gene related protein from the dorsal spinal cord was constant throughout the time points examined, changes occurred in the release of peptide evoked by 10 microM capsaicin. The capsaicin-evoked release of immunoreactive substance P was decreased at 6 h and eight days post-injection of adjuvant.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Linkage of cardiac left-right asymmetry and dorsal-anterior development in Xenopus.

The left-right body axis is defined relative to the dorsal-ventral and anterior-posterior body axes. Since left-right asymmetries are not randomly oriented with respect to dorsal-ventral and anterior-posterior spatial patterns, it is possible that a common mechanism determines all three axes in a coordinate manner. Two approaches were undertaken to determine whether alteration in dorsal-anterior development perturbs the left-right orientation of heart looping. Treatments known to decrease dorsal-anterior development in Xenopus laevis, UV irradiation during the first cell cycle or Xwnt-8 DNA injections into dorsal blastomeres, caused an increase in cardiac left-right reversals. The frequency of left-right reversal was correlated with the severity of dorsal-anterior perturbation and with the extent of anterior notochord regression. Injection of Xwnt-8 DNA into dorsal midline cells resulted in decreased dorsal-anterior development and a correlated increase in cardiac left-right reversals. In contrast, injection of Xwnt-8 DNA into cardiac progenitor blastomeres did not result in left-right reversals, and dorsal-anterior development and notochord formation were normal. Disrupting development of dorsal-anterior cells, including cells that give rise to the Organizer region and the notochord, results in the randomization of cardiac left-right asymmetry. These results suggest dorsal-anterior development and the regulation of left-right orientation are linked.

Animals↗
PubMed1992

Regulation of vertebrate left-right asymmetries by extracellular matrix.

The vertebrate body is organized along three geometric axes: anterior-posterior, dorsal-ventral and left-right. Left-right axis formation, displayed in heart and gut development, is the least understood, even though it has been studied for many years. In Xenopus laevis gastrulae, a fibronectin-rich extracellular matrix is deposited on the basal surface of ectoderm cells over which cardiac and visceral primordia move during development. Here I report experiments in which localized perturbation of a small patch of extracellular matrix by microsurgery was correlated with localized randomization of left-right asymmetries. Global perturbation of the extracellular matrix by microinjection of Arg-Gly-Asp peptides or heparinase into the blastocoel resulted in global randomization of left-right asymmetries. From these observations, I suggest that left-right axial information is contained in the extracellular matrix early in development and is independently transmitted to cardiac and visceral primordia.

Amino Acid Sequence↗
PubMed1991

Development of the left-right axis in amphibians.

The heart and viscera of vertebrates are formed from primordia that are apparently bilaterally symmetrical. This symmetry is broken during development, yielding organs that develop characteristic asymmetries along the left-right axis. Results from three lines of experimentation on embryos of the amphibian Xenopus laevis indicate that left-right asymmetries are established early in development and that cellular interactions transmit left-right information from one primordium to another. First, a cytoplasmic rearrangement that occurs during the first cell cycle after fertilization may establish left-right asymmetry in some regions of the embryo. Second, a variety of experimental results indicate that embryonic ectoderm or its basal extracellular matrix may transmit left-right axial information to cardiac mesoderm and visceral endoderm. Third, inhibition of proteoglycan synthesis during a narrow period of development, concurrent with the migration of the cardiac primordia to the ventral midline, prevents asymmetrical development of the heart.

Amphibians↗