Bruce P Brandhorst

Publications (76) View all

• Article: Oral-aboral patterning and gastrulation of sea urchin embryos depend on sulfated glycosaminoglycans.

  Karl-Frederik Bergeron, Xing Xu, Bruce P Brandhorst
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  ABSTRACT: Glycosaminoglycans (GAGs) are a heavily sulfated component of the extracellular matrix (ECM) implicated in a variety of cell signaling events involved in patterning of embryos. Embryos of the sea urchin Strongylocentrotus purpuratus were exposed to several inhibitors that disrupt GAG function during development. Treatment with chlorate, a general inhibitor of sulfation that leads to undersulfated GAGs, reduced sulfation of the urchin blastocoelar ECM. It also prevented correct specification of the oral-aboral axis and mouth formation, resulting in a radialized phenotype characterized by the lack of an oral field, incomplete gastrulation and formation of multiple skeletal spicule rudiments. Oral markers were initially expressed in most of the prospective ectoderm of chlorate-treated early blastulae, but then declined as aboral markers became expressed throughout most of the ectoderm. Nodal expression in the presumptive oral field is necessary and sufficient to specify the oral-aboral axis in urchins. Several lines of evidence suggest a deregulation of Nodal signaling is involved in the radialization caused by chlorate: (1) Radial embryos resemble those in which Nodal expression was knocked down. (2) Chlorate disrupted localized nodal expression in oral ectoderm, even when applied after the oral-aboral axis is specified and expression of other oral markers is resistant to treatment. (3) Inhibition with SB-431542 of ALK-4/5/7 receptors that mediate Nodal signaling causes defects in ectodermal patterning similar to those caused by chlorate. (4) Intriguingly, treatment of embryos with a sub-threshold dose of SB-431542 rescued the radialization caused by low concentrations of chlorate. Our results indicate important roles for sulfated GAGs in Nodal signaling and oral-aboral axial patterning, and in the cellular processes necessary for archenteron extension and mouth formation during gastrulation. We propose that interaction of the Nodal ligand with sulfated GAGs limits its diffusion, and is required to specify an oral field in the urchin embryo and organize the oral-aboral axis.
  Mechanisms of development 11/2010; 128(1-2):71-89. · 2.83 Impact Factor
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  Available from: Bruce P Brandhorst

  Article: The use of fresh embryos in stem cell research: ethical and policy issues.

  Cynthia B Cohen, Bruce Brandhorst, Andras Nagy, Arthur Leader, Bernard Dickens, Rosario M Isasi, Donald Evans, Bartha M Knoppers
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  ABSTRACT: Fresh embryos resulting from in vitro fertilization, including many of poor quality, can provide sources of human embryonic stem cell lines. We consider why some donate such embryos for this research, address relevant ethical and policy issues, and present core guidelines for fresh embryo donation based on those of Canada.
  Cell stem cell 06/2008; 2(5):416-21. · 23.56 Impact Factor
• Article: Interspecific variation in metamorphic competence in marine invertebrates: the significance for comparative investigations into the timing of metamorphosis.

  Cory D Bishop, Megan J Huggett, Andreas Heyland, Jason Hodin, Bruce P Brandhorst
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  ABSTRACT: Metamorphosis in marine invertebrate larvae is a dynamic, environmentally dependent process that integrates ontogeny with habitat selection. The capacity of many marine invertebrate larvae to survive and maintain metamorphic competence in the absence of environmental cues has been hypothesized to be an adaptive convergence (Hadfield and others 2001). A survey of the literature reveals that a single generalized hypothesis about metamorphic competence as an adaptive convergence is not sufficient to account for interspecific variation in this character. In an attempt to capture this variation, we discuss the "desperate larva hypothesis" and propose two additional hypotheses called the "variable retention hypothesis" and the "death before dishonor hypothesis." To validate these additional hypotheses we collected data on taxa from the published literature and performed a contingency analysis to detect correlations between spontaneous metamorphosis, habitat specificity and/or larval life-history mode, three characters relevant to environmentally induced settlement and metamorphosis. In order to account for phylogenetic bias in these correlations, we also constructed a phylogeny of these taxa and again performed a character-correlation analysis. Both these tests suggest that juvenile habitat specificity is correlated to the capacity of individuals to retain the competent larval state in the absence of substrate cues and therefore validate the existence of more than one hypothesis about metamorphic competence. We provide new data from the sea urchin Lytechinus pictus that suggest that nitric oxide (NO) and thyroxine hormone signaling interact to determine the probability of settlement in response to a settlement cue. Similarly, we provide evidence that thyroxine signaling in the sand dollar Dendraster excentricus increases spontaneous metamorphosis in the absence of cues from adult conspecifics in a manner that is independent of larval age.
  Integrative and Comparative Biology 12/2006; 46(6):662-82. · 2.45 Impact Factor
• Article: Synthesis and decay rates of major classes of deoxyribonucleic acid-like ribonucleic acid in sea urchin embryos

  Bruce P. Brandhorst, Tom Humphreys
  04/2002;
• Article: Sex-specific recombination rates in zebrafish (Danio rerio).

  Amy Singer, Hodel Perlman, YiLin Yan, Charlene Walker, Graham Corley-Smith, Bruce Brandhorst, John Postlethwait
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  ABSTRACT: In many organisms, the rate of genetic recombination is not uniform along the length of chromosomes or between sexes. To compare the relative recombination rates during meiosis in male and female zebrafish, we constructed a genetic map based on male meiosis. We developed a meiotic mapping panel of 94 androgenetic haploid embryos that were scored for genetic polymorphisms. The resulting male map was compared to female and sex-average maps. We found that the recombination rate in male meiosis is dramatically suppressed relative to that of female meiosis, especially near the centromere. These findings have practical applications for experimental design. The use of exclusively female meiosis in a positional cloning project maximizes the ratio of genetic map distance to physical distance. Alternatively, the use of exclusively male meiosis to localize a mutation initially to a linkage group or to maintain relationships of linked alleles minimizes recombination, thereby facilitating some types of analysis.
  Genetics 03/2002; 160(2):649-57. · 4.01 Impact Factor