835,739 research outputs found

    Positional information, positional error, and read-out precision in morphogenesis: a mathematical framework

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    The concept of positional information is central to our understanding of how cells in a multicellular structure determine their developmental fates. Nevertheless, positional information has neither been defined mathematically nor quantified in a principled way. Here we provide an information-theoretic definition in the context of developmental gene expression patterns and examine which features of expression patterns increase or decrease positional information. We connect positional information with the concept of positional error and develop tools to directly measure information and error from experimental data. We illustrate our framework for the case of gap gene expression patterns in the early Drosophila embryo and show how information that is distributed among only four genes is sufficient to determine developmental fates with single cell resolution. Our approach can be generalized to a variety of different model systems; procedures and examples are discussed in detail

    The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle.

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    In the mammalian ovary, great interest in the expression and function of the bone morphogenetic protein (BMP) family has been recently generated from evidence of their critical role in determining folliculogenesis and female fertility. Despite extensive work, there is a need to understand the cellular sites of expression of these important regulatory molecules, and how their gene expression changes within the basic ovary cell types through the cycle. Here we have performed a detailed in situ hybridization analysis of the spatial and temporal expression patterns of the BMP ligands (BMP-2, -3, -3b, -4, -6, -7, -15), receptors (BMPR-IA, -IB, -II), and BMP antagonist, follistatin, in rat ovaries over the normal estrous cycle. We have found that: i) all of the mRNAs are expressed in a cell-specific manner in the major classes of ovary cell types (oocyte, granulosa, theca interstitial, theca externa, corpora lutea, secondary interstitial, vascular and ovary surface epithelium); and ii) most undergo dynamic changes during follicular and corpora luteal morphogenesis and histogenesis. The general principle to emerge from these studies is that the developmental programs of folliculogenesis (recruitment, selection, atresia), ovulation, and luteogenesis (luteinization, luteolysis) are accompanied by rather dramatic spatial and temporal changes in the expression patterns of these BMP genes. These results lead us to hypothesize previously unanticipated roles for the BMP family in determining fundamental developmental events that ensure the proper timing and developmental events required for the generation of the estrous cycle

    Expression profiling of snoRNAs in normal hematopoiesis and AML

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    Key Points A subset of snoRNAs is expressed in a developmental- and lineage-specific manner during human hematopoiesis. Neither host gene expression nor alternative splicing accounted for the observed differential expression of snoRNAs in a subset of AML.</jats:p

    Finding the center reliably: robust patterns of developmental gene expression

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    We investigate a mechanism for the robust identification of the center of a developing biological system. We assume the existence of two morphogen gradients, an activator emanating from the anterior, and a co-repressor from the posterior. The co-repressor inhibits the action of the activator in switching on target genes. We apply this system to Drosophila embryos, where we predict the existence of a hitherto undetected posterior co-repressor. Using mathematical modelling, we show that a symmetric activator-co-repressor model can quantitatively explain the precise mid-embryo expression boundary of the hunchback gene, and the scaling of this pattern with embryo size.Comment: 4 pages, 3 figure

    Global Gene Expression Profiling of Individual Human Oocytes and Embryos Demonstrates Heterogeneity in Early Development

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    Early development in humans is characterised by low and variable embryonic viability, reflected in low fecundity and high rates of miscarriage, relative to other mammals. Data from assisted reproduction programmes provides additional evidence that this is largely mediated at the level of embryonic competence and is highly heterogeneous among embryos. Understanding the basis of this heterogeneity has important implications in a number of areas including: the regulation of early human development, disorders of pregnancy, assisted reproduction programmes, the long term health of children which may be programmed in early development, and the molecular basis of pluripotency in human stem cell populations. We have therefore investigated global gene expression profiles using polyAPCR amplification and microarray technology applied to individual human oocytes and 4-cell and blastocyst stage embryos. In order to explore the basis of any variability in detail, each developmental stage is replicated in triplicate. Our data show that although transcript profiles are highly stage-specific, within each stage they are relatively variable. We describe expression of a number of gene families and pathways including apoptosis, cell cycle and amino acid metabolism, which are variably expressed and may be reflective of embryonic developmental competence. Overall, our data suggest that heterogeneity in human embryo developmental competence is reflected in global transcript profiles, and that the vast majority of existing human embryo gene expression data based on pooled oocytes and embryos need to be reinterpreted

    Genomic Analysis of Drosophila Neuronal Remodeling: A Role for the RNA-Binding Protein Boule as a Negative Regulator of Axon Pruning

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    Drosophila mushroom body (MB) {gamma} neurons undergo axon pruning during metamorphosis through a process of localized degeneration of specific axon branches. Developmental axon degeneration is initiated by the steroid hormone ecdysone, acting through a nuclear receptor complex composed of USP (ultraspiracle) and EcRB1 (ecdysone receptor B1) to regulate gene expression in MB {gamma} neurons. To identify ecdysone-dependent gene expression changes in MB {gamma} neurons at the onset of axon pruning, we use laser capture microdissection to isolate wild-type and mutant MB neurons in which EcR (ecdysone receptor) activity is genetically blocked, and analyze expression changes by microarray. We identify several molecular pathways that are regulated in MB neurons by ecdysone. The most striking observation is the upregulation of genes involved in the UPS (ubiquitin–proteasome system), which is cell autonomously required for {gamma} neuron pruning. In addition, we characterize the function of Boule, an evolutionarily conserved RNA-binding protein previously implicated in spermatogenesis in flies and vertebrates. boule expression is downregulated by ecdysone in MB neurons at the onset of pruning, and forced expression of Boule in MB {gamma} neurons is sufficient to inhibit axon pruning. This activity is dependent on the RNA-binding domain of Boule and a conserved DAZ (deleted in azoospermia) domain implicated in interactions with other RNA-binding proteins. However, loss of Boule does not result in obvious defects in axon pruning or morphogenesis of MB neurons, suggesting that it acts redundantly with other ecdyonse-regulated genes. We propose a novel function for Boule in the CNS as a negative regulator of developmental axon pruning

    ZBED4, a cone and Müller cell protein in human retina, has a different cellular expression in mouse.

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    PurposeZBED4, a protein in cones and Müller cells of human retina, may play important functions as a transcriptional activator of genes expressed in those cells or as a co-activator/repressor of their nuclear hormone receptors. To begin investigating these potential roles of ZBED4, we studied the developmental expression and localization of both the Zbed4 mRNA and protein of mouse retina.Methodsnorthern blots showed the presence of Zbed4 mRNA in retina and other mouse tissues, and western blots showed the nuclear and cytoplasmic expression of Zbed4 at different developmental times. Antibodies against Zbed4 and specific retinal cell markers were used for retinal immunohistochemistry.ResultsZbed4 mRNA was present at different levels in all the mouse tissues analyzed. The Zbed4 protein was barely detectable at embryonic day (E)14.5 but was clearly seen at E16 at both retinal outer and vitreal borders and throughout the retina by E18 and postnatal day 0 (P0). Thereafter, Zbed4 expression was more restricted to the inner retina. While ZBED4 is localized in cones and endfeet of Müller cells of human retina, in adult mouse retina Zbed4 is only detected in Müller cell endfeet and processes. The same localization of Zbed4 was observed in rat retina. In early development, Zbed4 is mainly present in the nuclear fraction of the mouse retina, and in adulthood it becomes more enriched in the cytoplasmic fraction.ConclusionsThe patterns of spatial and temporal expression of Zbed4 in the mouse retina suggest a possible involvement of this protein in retinal morphogenesis and Müller cell function
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