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H Joseph Yost

Publications and source records attributed to H Joseph Yost.

8 recordsLinked to original sources

Cardiac neural crest contributes to cardiomyogenesis in zebrafish.

In birds and mammals, cardiac neural crest is essential for heart development and contributes to conotruncal cushion formation and outflow tract septation. The zebrafish prototypical heart lacks outflow tract septation, raising the question of whether cardiac neural crest exists in zebrafish. Here, results from three distinct lineage-labeling approaches identify zebrafish cardiac neural crest cells and indicate that these cells have the ability to generate MF20-positive muscle cells in the myocardium of the major chambers during development. Fate-mapping demonstrates that cardiac neural crest cells originate both from neural tube regions analogous to those found in birds, as well as from a novel region rostral to the otic vesicle. In contrast to other vertebrates, cardiac neural crest invades the myocardium in all segments of the heart, including outflow tract, atrium, atrioventricular junction, and ventricle in zebrafish. Three distinct groups of premigratory neural crest along the rostrocaudal axis have different propensities to contribute to different segments in the heart and are correspondingly marked by unique combinations of gene expression patterns. Zebrafish will serve as a model for understanding interactions between cardiac neural crest and cardiovascular development.

Animals↗

Genetics of human laterality disorders: insights from vertebrate model systems.

Many internal organs in the vertebrate body are asymmetrically oriented along the left-right (L-R) body axis. Organ asymmetry and some components of the molecular signaling pathways that direct L-R development are highly conserved among vertebrate species. Although individuals with full reversal of organ L-R asymmetry (situs inversus totalis) are healthy, significant morbidity and mortality is associated with perturbations in laterality that result in discordant orientation of organ systems and complex congenital heart defects. In humans and other vertebrates, genetic alterations of L-R signaling pathways can result in a wide spectrum of laterality defects. In this review we categorize laterality defects in humans, mice, and zebrafish into specific classes based on altered patterns of asymmetric gene expression, organ situs defects, and midline phenotypes. We suggest that this classification system provides a conceptual framework to help consolidate the disparate laterality phenotypes reported in humans and vertebrate model organisms, thereby refining our understanding of the genetics of L-R development. This approach helps suggest candidate genes and genetic pathways that might be perturbed in human laterality disorders and improves diagnostic criteria.

Animals↗

PKCgamma regulates syndecan-2 inside-out signaling during xenopus left-right development.

The transmembrane proteoglycan syndecan-2 cell nonautonomously regulates left-right (LR) development in migrating mesoderm by an unknown mechanism, leading to LR asymmetric gene expression and LR orientation of the heart and gut. Here, we demonstrate that protein kinase C gamma (PKCgamma) mediates phosphorylation of the cytoplasmic domain of syndecan-2 in right, but not left, animal cap ectodermal cells. Notably, both phosphorylation states of syndecan-2 are obligatory for normal LR development, with PKCgamma-dependent phosphorylated syndecan-2 in right ectodermal cells and nonphosphorylated syndecan-2 in left cells. The ectodermal cells contact migrating mesodermal cells during early gastrulation, concurrent with the transmission of LR information. This precedes the appearance of monocilia and is one of the earliest steps of LR development. These results demonstrate that PKCgamma regulates the cytoplasmic phosphorylation of syndecan-2 and, consequently, syndecan-2-mediated inside-out signaling to adjacent cells.

Animals↗

Lefty-dependent inhibition of Nodal- and Wnt-responsive organizer gene expression is essential for normal gastrulation.

During gastrulation, diffusible "organizer" signals, including members of the TGFbeta Nodal subfamily, pattern dorsal mesoderm and the embryonic axes. Simultaneously, negative regulators of these signals, including the Nodal inhibitor Lefty, an atypical TGFbeta factor, are induced by Nodal. This suggests that Lefty-dependent modulation of organizer signaling might regulate dorsal mesoderm patterning and axial morphogenesis. Here, Xenopus Lefty (Xlefty) function was blocked by injection of anti-Xlefty morpholino oligonucleotides (MO). Xlefty-deficient embryos underwent exogastrulation, an aberrant morphogenetic process not predicted from deregulation of the Nodal pathway alone. In the absence of Xlefty, both Nodal- (Xnr2, gsc, cer, Xbra) and Wnt-responsive (gsc, Xnr3) organizer gene expression expanded away from the dorsal blastopore lip. Conversely, coexpression of Xlefty with Nodal or Wnt reduced the ectopic expression of Nodal- (Xbra) and Wnt-responsive (Xnr3) genes in a dose-dependent manner. Furthermore, Xlefty expression in the ectodermal animal pole inhibited endogenous Nodal- and Wnt-responsive gene expression in distant mesoderm cells, indicating that Xlefty inhibition can spread from its source. We hypothesize that Xlefty negatively regulates the spatial extent of Nodal- and Wnt-responsive gene expression in the organizer and that this Xlefty-dependent inhibition is essential for normal organizer patterning and gastrulation.

Activins↗

Conserved function for embryonic nodal cilia.

How left right handedness originates in the body plan of the developing vertebrate embryo is a subject of considerable debate. In mice, a left right bias is thought to arise from a directional extracellular flow (nodal flow) that is generated by dynein-dependent rotation of monocilia on the ventral surface of the embryonic node. Here we show that the existence of node monocilia and the expression of a dynein gene that is implicated in ciliary function are conserved across a wide range of vertebrate classes, indicating that a similar ciliary mechanism may underlie the establishment of handedness in all vertebrates.

Animals↗

The left-right determinant inversin has highly conserved ankyrin repeat and IQ domains and interacts with calmodulin.

All vertebrates have a left-right body axis with invariant asymmetries of the heart and the positions of the abdominal viscera. Major advances have recently been made in defining molecular components of the pathway specifying the vertebrate left-right axis, but our knowledge of the early determinants is extremely limited. In the invmouse the left-right axis is consistently reversed, unlike other vertebrate mutants where randomisation of situs is apparent. The gene disrupted in this mouse encodes a 1062-amino-acid protein, inversin. We previously reported 16 tandem ankyrin repeats, spanning amino acids 13-557, and two putative nuclear localisation sequences, but otherwise the sequence offered few clues to the possible function. In order to identify regions likely to be functionally important, we have identified and characterised orthologous sequences in several species, including chick, Xenopus and zebrafish. Sequence comparisons show strong conservation of the ankyrin repeat region and also a lysine-rich domain spanning amino acids 558-604. Further analysis identified a highly conserved IQ calmodulin-binding domain in the latter region and another such domain in an otherwise poorly conserved C-terminal region. A yeast two-hybrid screen identified calmodulin in one third of the positive clones, and we confirmed this interaction by immunoprecipitation.

Amino Acid Sequence↗

Ectodermal syndecan-2 mediates left-right axis formation in migrating mesoderm as a cell-nonautonomous Vg1 cofactor.

Heparan sulfate proteoglycans expressed on the Xenopus animal cap ectoderm have been implicated in transmitting left-right information to heart and gut primordia. We report here that syndecan-2 functions in the ectoderm to mediate cardiac and visceral situs, upstream of known asymmetrically expressed genes but independently of its ability to mediate fibronectin fibrillogenesis. Left-right development is dependent on a distinct subset of glycosaminoglycan attachment sites on syndecan-2. A novel in vivo approach with enterokinase demonstrates that syndecan-2 functions in left-right patterning during early gastrulation. We describe a cell-nonautonomous role for ectodermal syndecan-2 in transmitting left-right information to migrating mesoderm. The results further suggest that this function may be related to the transduction of Vg1-related signals.

Activin Receptors, Type I↗