title: Embryonic maturation of epidermal Merkel cells is controlled by a redundant transcription factor network.
abstract: Merkel cell-neurite complexes are located in touch-sensitive areas of the mammalian skin and are involved in recognition of the texture and shape of objects. Merkel cells are essential for these tactile discriminations, as they generate action potentials in response to touch stimuli and induce the firing of innervating afferent nerves. It has been shown that Merkel cells originate from epidermal stem cells, but the cellular and molecular mechanisms of their development are largely unknown. In this study, we analyzed Merkel cell differentiation during development and found that it is a temporally regulated maturation process characterized by a sequential activation of Merkel cell-specific genes. We uncovered key transcription factors controlling this process and showed that the transcription factor Atoh1 is required for initial Merkel cell specification. The subsequent maturation steps of Merkel cell differentiation are controlled by cooperative function of the transcription factors Sox2 and Isl1, which physically interact and work to sustain Atoh1 expression. These findings reveal the presence of a robust transcriptional network required to produce functional Merkel cells that are required for tactile discrimination.
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Carolina N
authors.initials: CN
authors.lastname: Perdigoto
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Evan S
authors.initials: ES
authors.lastname: Bardot
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Valdes
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Santoriello
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA elena.ezhkova@mssm.edu.
authors.forename: Elena
authors.initials: E
authors.lastname: Ezhkova
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000235:genetics / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D007211:Indoles; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D018862:Merkel Cells / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000196:embryology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D007211:Indoles; D060850:LIM-Homeodomain Proteins; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; C500943:Atoh1 protein, mouse; C527783:Sox2 protein, mouse; C063843:insulin gene enhancer binding protein Isl-1; C007293:DAPI
keywords: Merkel cells; Mouse; Skin; Stem cells