95 research outputs found

    Yap and Taz regulate retinal pigment epithelial cell fate

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    The optic vesicle comprises a pool of bi-potential progenitor cells from which the retinal pigment epithelium (RPE) and neural retina fates segregate during ocular morphogenesis. Several transcription factors and signaling pathways have been shown to be important for RPE maintenance and differentiation, but an understanding of the initial fate specification and determination of this ocular cell type is lacking. We show that Yap/Taz-Tead activity is necessary and sufficient for optic vesicle progenitors to adopt RPE identity in zebrafish. A Tead-responsive transgene is expressed within the domain of the optic cup from which RPE arises, and Yap immunoreactivity localizes to the nuclei of prospective RPE cells. yap (yap1) mutants lack a subset of RPE cells and/or exhibit coloboma. Loss of RPE in yap mutants is exacerbated in combination with taz (wwtr1) mutant alleles such that, when Yap and Taz are both absent, optic vesicle progenitor cells completely lose their ability to form RPE. The mechanism of Yap-dependent RPE cell type determination is reliant on both nuclear localization of Yap and interaction with a Tead co-factor. In contrast to loss of Yap and Taz, overexpression of either protein within optic vesicle progenitors leads to ectopic pigmentation in a dosage-dependent manner. Overall, this study identifies Yap and Taz as key early regulators of RPE genesis and provides a mechanistic framework for understanding the congenital ocular defects of Sveinsson's chorioretinal atrophy and congenital retinal coloboma

    Crk and CrkL adaptor proteins: networks for physiological and pathological signaling

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    The Crk adaptor proteins (Crk and CrkL) constitute an integral part of a network of essential signal transduction pathways in humans and other organisms that act as major convergence points in tyrosine kinase signaling. Crk proteins integrate signals from a wide variety of sources, including growth factors, extracellular matrix molecules, bacterial pathogens, and apoptotic cells. Mounting evidence indicates that dysregulation of Crk proteins is associated with human diseases, including cancer and susceptibility to pathogen infections. Recent structural work has identified new and unusual insights into the regulation of Crk proteins, providing a rationale for how Crk can sense diverse signals and produce a myriad of biological responses

    Cultural transmission and biological markets

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    Active cultural transmission of fitness-enhancing behavior (sometimes called “teaching”) can be seen as a costly strategy: one for which its evolutionary stability poses a Darwinian puzzle. In this article, we offer a biological market model of cultural transmission that substitutes or complements existing kin selection-based proposals for the evolution of cultural capacities. We explicitly demonstrate how a biological market can account for the evolution of teaching when individual learners are the exclusive focus of social learning (such as in a fast-changing environment). We also show how this biological market can affect the dynamics of cumulative culture. The model works best when it is difficult to have access to the observation of the behavior without the help of the actor. However, in contrast to previous non-mathematical hypotheses for the evolution of teaching, we show how teaching evolves even when innovations are insufficiently opaque and therefore vulnerable to acquisition by emulators via inadvertent transmission. Furthermore, teaching in a biological market is an important precondition for enhancing individual learning abilitie

    Ontogeny of Stress Reactivity in the Human Child: Phenotypic Flexibility, Trade-Offs, and Pathology

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    Fluid flow in shear zones: insights from the geometry and evolution of ore bodies at Renco gold mine, Zimbabwe

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    The geometry of mineral deposits can give insights into fluid flow in shear zones. Lode gold ore bodies at Renco Mine, in the Limpopo Belt, Zimbabwe, occur as siliceous breccias and mylonites within amphibolite facies shear zones that dip either gently or steeply. The two sets of ore bodies formed synchronously from hydrothermal fluids. The ore bodies are oblate, but have well-defined long axes. Larger ore bodies are more oblate. High-grade gold ore shoots have long axes that plunge down dip; this direction is perpendicular to the long axes of the low-grade ore bodies. The centres of the high-grade ore bodies align within the low-grade ore bodies along strike in both gently and steeply dipping groups. The range of sizes and shapes of the ore bodies are interpreted as a growth sequence. Geometrical models are proposed for the gently and steeply dipping ore bodies, in which individual ore bodies grow with long axes plunging down dip, and merge to form larger, more oblate ore bodies. The models show that when three or more ore bodies coalesce, the long axis of the merged ore body is perpendicular to the component ore bodies, and that ore bodies in the deposit may have a range of shapes due to both growth of individual ore bodies, and their coalescence. The long axes of the high-grade ore bodies are parallel to the shear directions of both the gently and steeply dipping dip slip shear zones, which were the directions of greatest permeability and fluid flow. The larger, lower grade bodies, which may have formed by coalescence, are elongate perpendicular to these directions
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