Notch pathway signaling in the skin antagonizes Merkel cell development

Developmental biology

Adam C. Kubicki^1¹  Margaret C. Wright^3²  Gregory J. Logan^1,2³ 

[1] Center for Neurosciences, University of Pittsburgh, Pittsburgh, PA 15260, United States^3;Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, United States^2;Richard King Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh Medical Center, Pittsburgh, PA 15224, United States^1

关键词: Somatosensation;    Skin;    Development;   

DOI  :  10.1016/j.ydbio.2017.12.007

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Merkel cells are mechanosensitive skin cells derived from the epidermal lineage whose development requires expression of the basic helix-loop-helix transcription factor Atoh1. The genes and pathways involved in regulating Merkel cell development during embryogenesis are poorly understood. Notch pathway signaling antagonizes Atoh1 expression in many developing body regions, so we hypothesized that Notch signaling might inhibit Merkel cell development. We found that conditional, constitutive overexpression of the Notch intracellular domain (NICD) in mouse epidermis significantly decreased Merkel cell numbers in whisker follicles and touch domes of hairy skin. Conversely, conditional deletion of the obligate NICD binding partner RBPj in the epidermis significantly increased Merkel cell numbers in whisker follicles, led to the development of ectopic Merkel cells outside of touch domes in hairy skin epidermis, and altered the distribution of Merkel cells in touch domes. Deletion of the downstream Notch effector gene Hes1 also significantly increased Merkel cell numbers in whisker follicles. Together, these data demonstrate that Notch signaling regulates Merkel cell production and patterning.

【 授权许可】

CC BY