Scientists use zebrafish to study how Merkel cells develop

Rákkutatás · Merkel cell carcinoma

Dendritic Merkel cells (dMCs) are an intermediate progenitor that mature into fully differentiated Merkel cells, and Ectodysplasin A signaling regulates their final morphology.

Sensory cells often adopt specific morphologies that aid in the detection of external stimuli. Merkel cells encode gentle touch stimuli in vertebrate skin and adopt a reproducible shape characterized by spiky actin-rich microvilli that emanate from the cell surface. The mechanisms by which Merkel cells acquire this stereotyped morphology from keratinocyte progenitors are unknown. Here, we establish that dendritic Merkel cells (dMCs) express atonal homolog 1a (atoh1a), extend dynamic filopodial processes, and arise in transient waves during zebrafish skin development and regeneration. We find that dMCs share molecular similarities with both basal keratinocytes and Merkel cells, yet display mesenchymal-like behaviors, including local cell motility and proliferation within the epidermis. Furthermore, dMCs can directly adopt the mature, microvilliated Merkel cell morphology through substantial remodeling of the actin cytoskeleton. Loss of Ectodysplasin A signaling alters the morphology of dMCs and Merkel cells within specific skin regions. Our results show that dMCs represent an intermediate state in the Merkel cell maturation program and identify Ectodysplasin A signaling as a key regulator of Merkel cell morphology.

Understanding the maturation pathway of Merkel cells and the role of Ectodysplasin A signaling could reveal how Merkel cell carcinoma originates and spreads, potentially guiding new therapeutic strategies.

Bizonyítékszint: Klinikai vizsgálat. Formális klinikai vizsgálati eredmény.

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