33 research outputs found

    Degeneration and Regeneration in the Vertebrate Retina

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    International audienceThe human retina is a complex, layered tissue responsible for the perception of the visual stimuli coming from the external environment. Since the visual inputs account for about 30% of our sensory stimulations, it is not surprising that partial or complete blindness results in a strong decrease of life quality. Several diseases affect the retina, often leading to degeneration of one or several cell types. The damage induced by these diseases is often irreversible, thus leading to a permanent loss of the visual ability. Over the last decades significant progress has been made to elucidate the molecular basis of retinal degenerative diseases. This knowledge is necessary in order to design valid approaches for the treatment of retinopathies

    Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2

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    The mammalian intestine is one of the most rapidly self-renewing tissues, driven by stem cells residing at the crypt bottom. Paneth cells form a major element of the niche microenvironment providing various growth factors to orchestrate intestinal stem cell homeostasis, such as Wnt3. Different Wnt ligands can selectively activate β-catenin-dependent (canonical) or -independent (noncanonical) signaling. Here, we report that the Dishevelled-associated activator of morphogenesis 1 (Daam1) and its paralogue Daam2 asymmetrically regulate canonical and noncanonical Wnt (Wnt/PCP) signaling. Daam1/2 interacts with the Wnt inhibitor RNF43, and Daam1/2 double knockout stimulates canonical Wnt signaling by preventing RNF43-dependent degradation of the Wnt receptor, Frizzled (Fzd). Single-cell RNA sequencing analysis revealed that Paneth cell differentiation is impaired by Daam1/2 depletion because of defective Wnt/PCP signaling. Together, we identified Daam1/2 as an unexpected hub molecule coordinating both canonical and noncanonical Wnt, which is fundamental for specifying an adequate number of Paneth cells

    RNF43 and ZNRF3 in Wnt Signaling-A Master Regulator at the Membrane

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    The Wnt & beta;-catenin signaling pathway is a highly conserved mechanism that plays a critical role from embryonic development and adult stem cell homeostasis. However, dysregulation of the Wnt pathway has been implicated in various diseases, including cancer. Therefore, multiple layers of regulatory mechanisms tightly control the activation and suppression of the Wnt signal. The E3 ubiquitin ligases RNF43 and ZNRF3, which are known negative regulators of the Wnt pathway, are critical component of Wnt signaling regulation. These E3 ubiquitin ligases control Wnt signaling by targeting the Wnt receptor Frizzled to induce ubiquitination-mediated endo-lysosomal degradation, thus controlling the activation of the Wnt signaling pathway. We also discuss the regulatory mechanisms, interactors, and evolution of RNF43 and ZNRF3. This review article summarizes recent findings on RNF43 and ZNRF3 and their potential implications for the development of therapeutic strategies to target the Wnt signaling pathway in various diseases, including cancer.11Nsciescopu

    Development: scaling to size by protease inhibition.

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    The dorsal half of bisected Xenopus laevis embryos can regenerate a well-proportioned organism on a smaller scale. A new study indicates that the removal of ventral tissue generates a steeper Chordin gradient by reducing Sizzled, a secreted inhibitor of Tolloid chordinases
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