19 research outputs found

    Complexity galore:3D cultures, biomechanics and systems medicine at the eighth ENBDC workshop "Methods in Mammary Gland Development and Cancer"

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    The ENBDC workshop “Methods in Mammary Gland Development and Cancer” is an established international forum to showcase the latest technical advances in the field. The eighth meeting focused on emerging concepts and technologies for studying normal and neoplastic breast development

    Imagine beyond: recent breakthroughs and next challenges in mammary gland biology and breast cancer research

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    On 8 December 2022 the organizing committee of the European Network for Breast Development and Cancer labs (ENBDC) held its fifth annual Think Tank meeting in Amsterdam, the Netherlands. Here, we embraced the opportunity to look back to identify the most prominent breakthroughs of the past ten years and to reflect on the main challenges that lie ahead for our field in the years to come. The outcomes of these discussions are presented in this position paper, in the hope that it will serve as a summary of the current state of affairs in mammary gland biology and breast cancer research for early career researchers and other newcomers in the field, and as inspiration for scientists and clinicians to move the field forward

    Review TRENDS in Genetics Vol.22 No.12 Knockout mouse models to study Wnt signal transduction

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    Wnt signal transduction is crucial for maintaining the balance between proliferation and differentiation throughout embryogenesis and postnatal life. Here, we provide a comprehensive overview of the conventional knockout mouse studies of both the canonical and the noncanonical Wnt pathways during mammalian development. Many of these knockout mice display early embryonic lethality, underscoring the fundamental importance of Wnt signal transduction, but precluding functional analyses at later stages. Use of conditional or inducible mouse models will enable us to study the role of Wnt signaling during later stages of development and adult life. Furthermore, genomic-scale approaches and advanced imaging techniques could provide a means to start dissecting the mechanism behind the observed phenotypes. Studying Wnt signal transduction in mice The development of multicellular organisms requires the orchestrated activities of various signal transduction pathways to ensure control over processes governing cell proliferation, differentiation and survival. One of the signaling pathways crucial for embryonic development and for maintaining homeostatic tissue function is the Wnt pathway [1–3] (Box 1). Since the 1980s our knowledge of Wnt signal transduction has expanded tremendously. Detailed, current information on this pathway can be found on the Wnt Homepag

    Frat is dispensable for canonical Wnt signaling in mammals

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    Wnt-signal transduction through β-catenin is thought to require the inhibition of GSK3 by Frat/GBP. To investigate the role of Frat in mammalian development, we have generated mice with targeted mutations in all three murine Frat homologs. We show that Frat is normally expressed at sites of active Wnt signaling. Surprisingly, Frat-deficient mice do not display gross abnormalities. Moreover, canonical Wnt signaling in primary cells is unaffected by the loss of Frat. These studies show that Frat is not an essential component of the canonical Wnt pathway in higher organisms, despite the strict requirement of Frat/GBP for maternal Wnt signaling in Xenopus
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