Lrig1 and Wnt dependent niches dictate segregation of resident immune cells and melanocytes in murine tail epidermis

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

ABSTRACT The barrier-forming, self-renewing mammalian epidermis comprises keratinocytes, pigment- producing melanocytes, and resident immune cells as first-line host defense. In murine tail skin, interfollicular epidermis patterns into pigmented ′scale′ and hypopigmented ′interscale′ epidermis. Why and how mature melanocytes accumulate in scale epidermis is unresolved. Here, we delineate a cellular hierarchy among epidermal cell types that determines skin patterning. Already during postnatal development, melanocytes co-segregate with newly forming scale compartments. Intriguingly, this process coincides with partitioning of both Langerhans cells and dendritic epidermal T-cells to interscale epidermis, suggesting functional segregation of pigmentation and immune surveillance. Analysis of non-pigmented mice and of mice lacking melanocytes or resident immune cells revealed that immunocyte patterning is melanocyte- and melanin-independent, and, vice versa , immune cells do not control melanocyte localization. Instead, genetically enforced progressive scale fusion upon Lrig1 deletion showed that melanocytes and immune cells dynamically follow epithelial scale:interscale patterns. Importantly, disrupting Wnt-Lef1 function in keratinocytes caused melanocyte mislocalization to interscale epidermis, implicating canonical Wnt signaling in organizing the pigmentation pattern. Together, this work uncovered cellular and molecular principles underlying the compartmentalization of tissue functions in skin. SUMMARY STATEMENT Pigmentation and immune surveillance functions in murine tail skin are spatially segregated by Lrig1- and Wnt-Lef1-dependent keratinocyte lineages that control the partitioning of melanocytes and tissue-resident immune cells into distinct epidermal niches.

Authors 8

1. Susanne C. Baess

   University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · Saarland University

   Affiliation as printed

   Cell and Developmental Biology, Center of Human and Molecular Biology (ZHMB), Saarland University, Faculty of Medicine, Homburg/Saar, Germany

   Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany

   Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Germany

2. Ann-Kathrin Burkhart

   Saarland University

   Affiliation as printed

   Cell and Developmental Biology, Center of Human and Molecular Biology (ZHMB), Saarland University, Faculty of Medicine, Homburg/Saar, Germany

3. Sabrina Cappello

   Saarland University

   Affiliation as printed

   Cell and Developmental Biology, Center of Human and Molecular Biology (ZHMB), Saarland University, Faculty of Medicine, Homburg/Saar, Germany

4. Annika Graband

   University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · Saarland University

   Affiliation as printed

   Cell and Developmental Biology, Center of Human and Molecular Biology (ZHMB), Saarland University, Faculty of Medicine, Homburg/Saar, Germany

   Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany

   Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Germany

5. Kristin Seré Aachen Department of Cell Biology Institute for Biomedical Engineering

   RWTH Aachen University

   Affiliation as printed

   Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany

   Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, Aachen, Germany

6. Martin Zenke Aachen Department of Cell Biology Institute for Biomedical Engineering

   RWTH Aachen University

   Affiliation as printed

   Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany

   Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, Aachen, Germany

7. Catherin Niemann

   University of Cologne · University Hospital Cologne

   Affiliation as printed

   Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany

   Center of Biochemistry, Faculty of Medicine and University Hospital Cologne, Germany

8. Sandra Iden corresponding

   University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · Saarland University

   Affiliation as printed

   Cell and Developmental Biology, Center of Human and Molecular Biology (ZHMB), Saarland University, Faculty of Medicine, Homburg/Saar, Germany

   Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany

   Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Germany