Biomedical subjects

Julian L Wong

Publications and source records attributed to Julian L Wong.

6 recordsLinked to original sources

PubMed2006

Rendezvin: An essential gene encoding independent, differentially secreted egg proteins that organize the fertilization envelope proteome after self-association.

Preventing polyspermy during animal fertilization relies on modifications to the egg's extracellular matrix. On fertilization in sea urchins, the contents of cortical granules are secreted and rapidly assemble into the egg's extracellular vitelline layer, forming the fertilization envelope, a proteinaceous structure that protects the zygote from subsequent sperm. Here, we document rendezvin, a gene whose transcript is differentially spliced to yield proteins destined for either cortical granules or the vitelline layer. These distinctly trafficked variants reunite after cortical granule secretion at fertilization. Together, they help coordinate assembly of the functional fertilization envelope, whose proteome is now defined in full.

Alternative Splicing↗

PubMed2006

Oogenesis: single cell development and differentiation.

Oocytes express a unique set of genes that are essential for their growth, for meiotic recombination and division, for storage of nutrients, and for fertilization. We have utilized the newly sequenced genome of Strongylocentrotus purpuratus to identify genes that help the oocyte accomplish each of these tasks. This study emphasizes four classes of genes that are specialized for oocyte function: (1) Transcription factors: many of these factors are not significantly expressed in embryos, but are shared by other adult tissues, namely the ovary, testis, and gut. (2) Meiosis: A full set of meiotic genes is present in the sea urchin, including those involved in cohesion, in synaptonemal complex formation, and in meiotic recombination. (3) Yolk uptake and storage: Nutrient storage for use during early embryogenesis is essential to oocyte function in most animals; the sea urchin accomplishes this task by using the major yolk protein and a family of accessory proteins called YP30. Comparison of the YP30 family members across their conserved, tandem fasciclin domains with their intervening introns reveals an incongruence in the evolution of its major clades. (4) Fertilization: This set of genes includes many of the cell surface proteins involved in sperm interaction and in the physical block to polyspermy. The majority of these genes are active only in oocytes, and in many cases, their anatomy reflects the tandem repeating interaction domains essential for the function of these proteins. Together, the expression profile of these four gene classes highlights the transitions of the oocyte from a stem cell precursor, through stages of development, to the clearing and re-programming of gene expression necessary to transition from oocyte, to egg, to embryo.

Animals↗

PubMed2006

Defending the zygote: search for the ancestral animal block to polyspermy.

Fertilization is the union of a single sperm and an egg, an event that results in a diploid embryo. Animals use many mechanisms to achieve this ratio; the most prevalent involves physically blocking the fusion of subsequent sperm. Selective pressures to maintain monospermy have resulted in an elaboration of diverse egg and sperm structures. The processes employed for monospermy are as diverse as the animals that result from this process. Yet, the fundamental molecular requirements for successful monospermic fertilization are similar, implying that animals may have a common ancestral block to polyspermy. Here, we explore this hypothesis, reviewing biochemical, molecular, and genetic discoveries that lend support to a common ancestral mechanism. We also consider the evolution of alternative or radical techniques, including physiological polyspermy, with respect to our ability to describe a parsimonious guide to fertilization.

Animals↗

PubMed2005

Reactive oxygen species and Udx1 during early sea urchin development.

Sea urchin fertilization is marked by a massive conversion of molecular oxygen to hydrogen peroxide by a sea urchin dual oxidase, Udx1. This enzyme is essential for completing the physical block to polyspermy. Yet, its expression is maintained during development, as indicated by the presence of both Udx1 mRNA and Udx1 protein enriched at the surface of all non-mesenchymal blastomeres. When hydrogen peroxide synthesis by Udx1 is inhibited, either pharmacologically or by specific antibody injection, cleavage is delayed. Application of exogenous hydrogen peroxide, however, partially rescues a fraction of these defective embryos. We also report an unequal distribution of reactive oxygen species between sister blastomeres during early cleavage stages, suggesting a functional role for Udx1 in intracellular signaling.

Animals↗

PubMed2004

The oxidative burst at fertilization is dependent upon activation of the dual oxidase Udx1.

The sea urchin egg is a quiescent cell...until fertilization, when the egg is activated. The classic respiratory burst at fertilization is the result of prodigious hydrogen peroxide production, but the mechanism for this synthesis is not known. Here we quantitate the kinetics of hydrogen peroxide synthesis at a single-cell level using an imaging photon detector, showing that 60 nM hydrogen peroxide accumulates within the perivitelline space of each zygote. We find that the NADPH oxidation activity is enriched at the cell surface and is sensitive to a pharmacological inhibitor of NADPH oxidase enzymes. Finally, we show that a sea urchin dual oxidase homolog, Udx1, is responsible for generating the hydrogen peroxide necessary for the physical block to polyspermy. Phylogenetic analysis of the enzymatic modules in Udx1 suggests a potentially conserved role for the dual oxidase family in hydrogen peroxide production and regulation during fertilization.

Animals↗

PubMedDate not supplied

Major components of a sea urchin block to polyspermy are structurally and functionally conserved.

One sperm fusing with one egg is requisite for successful fertilization; additional sperm fusions are lethal to the embryo. Because sperm usually outnumber eggs, evolution has selected for mechanisms that prevent this polyspermy by immediately modifying the egg extracellular matrix. We focus here on the contribution of cortical granule contents in the sea urchin block to polyspermy to begin to understand how well this process is conserved. We identified each of the major constituents of the fertilization envelope in two species of seaurchins, Strongylocentrotus purpuratus and Lytechinus variegatus, that diverged 30 to 50 million years ago. Our results show that the five major structural components of the fertilization envelope, derived from the egg cortical granules, are semiconserved. Most of these orthologs share sequence identity and encode multiple low-density lipoprotein receptor type A repeats or CUB domains but at least two contain radically different carboxy-terminal repeats. Using a new association assay, we also show that these major structural components are functionally conserved during fertilization envelope construction. Thus, it seems that this population of female reproductive proteins has retained functional motifs while gaining significant sequence diversity-two opposing paths that may reflect cooperativity among the proteins that compose the fertilization envelope.

Animals↗