Stabilization of ß-catenin promotes melanocyte specification at the expense of the Schwann cell lineage.

The canonical Wnt/ß-catenin pathway governs a multitude of developmental processes in various cell lineages, including the melanocyte lineage. Indeed, ß-catenin regulates transcription of Mitf-M, the master regulator of this lineage. The first wave of melanocytes to colonize the skin is directly derived from neural crest cells, whereas the second wave of melanocytes is derived from Schwann cell precursors (SCPs). We investigated the influence of ß-catenin in the development of melanocytes of the first and second waves by generating mice expressing a constitutively active form of ß-catenin in cells expressing tyrosinase. Constitutive activation of ß-catenin did not affect the development of truncal melanoblasts but led to marked hyperpigmentation of the paws. By activating ß-catenin at various stages of development (E8.5-E11.5), we showed that the activation of ß-catenin in bipotent SCPs favored melanoblast specification at the expense of Schwann cells in the limbs within a specific temporal window. Furthermore, in vitro hyperactivation of the Wnt/ß-catenin pathway, which is required for melanocyte development, induces activation of Mitf-M, in turn repressing FoxD3 expression. In conclusion, ß-catenin overexpression promotes SCP cell fate decisions towards the melanocyte lineage.

European Healthy Hydration Awareness Campaign for Dietitians.

Up to 50% of the adult population fail to meet the recommended total water intake despite the adverse health outcomes associated with chronic low fluid intake. Total fluid intake plays an important role in the energy and nutrient intake of individuals. Dietitians' role is to advise and guide the population toward a healthier diet. However, based on existing evidence, dietitians' current knowledge and practices regarding healthy hydration is an area for improvement. The European Healthy Hydration Awareness Campaign (EuHHAC) is an initiative between the European Federation of the Associations of Dietitians (EFAD) and the Hydration and Health Department of Danone Research, which aims to increase knowledge and awareness of healthy hydration and provide dietitians with evidence-based resources to use in practice. Since 2016, a series of tasks were undertaken by the EuHHAC group targeting dietitians across Europe. These tasks included an online survey addressing gaps in hydration knowledge, a webinar providing information on the terminology and impact of hydration on health, an interactive session addressing facilitators and barriers to healthy hydration, and a tutorial summarizing key hydration information and take-home messages. Dietitians were actively engaged in each aspect. Based on the feedback received, awareness of hydration was increased among dietitians. To further enhance understanding, an online Hydration Resource Center, including the resources of EuHHAC, will be created and uploaded on the EFAD website. Once completed an evaluation study will be undertaken to assess the usefulness of the resources in practice. The deliverables will be cascaded across Europe and worldwide via social media, conferences, and publications.

Altered E-Cadherin Levels and Distribution in Melanocytes Precede Clinical Manifestations of Vitiligo.

Vitiligo is the most common depigmenting disorder resulting from the loss of melanocytes from the basal epidermal layer. The pathogenesis of the disease is likely multifactorial and involves autoimmune causes, as well as oxidative and mechanical stress. It is important to identify early events in vitiligo to clarify pathogenesis, improve diagnosis, and inform therapy. Here, we show that E-cadherin (Ecad), which mediates the adhesion between melanocytes and keratinocytes in the epidermis, is absent from or discontinuously distributed across melanocyte membranes of vitiligo patients long before clinical lesions appear. This abnormality is associated with the detachment of the melanocytes from the basal to the suprabasal layers in the epidermis. Using human epidermal reconstructed skin and mouse models with normal or defective Ecad expression in melanocytes, we demonstrated that Ecad is required for melanocyte adhesiveness to the basal layer under oxidative and mechanical stress, establishing a link between silent/preclinical, cell-autonomous defects in vitiligo melanocytes and known environmental stressors accelerating disease expression. Our results implicate a primary predisposing skin defect affecting melanocyte adhesiveness that, under stress conditions, leads to disappearance of melanocytes and clinical vitiligo. Melanocyte adhesiveness is thus a potential target for therapy aiming at disease stabilization.