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Black, E. C.

Publications and source records attributed to Black, E. C..

4 recordsLinked to original sources

Transcriptomic profiling identifies cellular and molecular transitions during Merkel cell regeneration

Skin exhibits a remarkable capacity for regeneration, which requires the coordinated reconstitution of diverse cell types and structures. Merkel cells are mechanosensory cells that detect gentle touch and develop in coordination with dermal appendages, yet Merkel cell regeneration remains incompletely understood. To investigate Merkel cell lineage dynamics during skin regeneration, we performed single-cell RNA sequencing of regenerating adult zebrafish skin after dermal appendage removal. We find that the regenerating Merkel cell lineage is heterogeneous and characterize molecular markers associated with Merkel cell subpopulations. Through cross-species analysis with mouse and human Merkel cells, we identify conserved elements of Merkel cell identity and function across vertebrates. Trajectory analysis reveals a continuous spectrum of transcriptional state transitions within the Merkel cell population, suggesting dynamic lineage progression during regeneration and involving an epithelial-to-mesenchymal-like transition. Finally, cell fate mapping and in vivo analysis identify a putative pool of cldna+ suprabasal keratinocyte progenitors that give rise to regenerating Merkel cells. Together, these findings establish a genome resource for studies of zebrafish skin regeneration and provide insights into Merkel cell heterogeneity, conservation, lineage relationships and regenerative dynamics.

developmental biology↗

Dendritic atoh1a+ cells serve as transient intermediates during zebrafish Merkel cell development and regeneration

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 mechanism by which Merkel cells acquire this stereotyped morphology from basal keratinocyte progenitors is 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.

developmental biology↗

Dermal appendage-dependent patterning of zebrafish atoh1a+ Merkel cells

Touch system function requires precise interactions between specialized skin cells and somatosensory axons, as exemplified by the vertebrate mechanosensory Merkel cell-neurite complex. Development and patterning of Merkel cells and associated neurites during skin organogenesis remains poorly understood, partly due to the in utero development of mammalian embryos. Here, we discover Merkel cells in the zebrafish epidermis and identify Atonal homolog 1a (Atoh1a) as a marker of zebrafish Merkel cells. We show that zebrafish Merkel cells derive from basal keratinocytes, express neurosecretory and mechanosensory machinery, extend actin-rich microvilli, and complex with somatosensory axons, all hallmarks of mammalian Merkel cells. Merkel cells populate all major adult skin compartments, with region-specific densities and distribution patterns. In vivo photoconversion reveals that Merkel cells undergo steady loss and replenishment during skin homeostasis. Merkel cells develop concomitant with dermal appendages along the trunk, and preventing dermal appendage formation reduces Merkel cell density by affecting both cell differentiation and maintenance. By contrast, altering dermal appendage morphology changes the distribution, but not density, of Merkel cells. Overall, our studies provide insights into touch system maturation during skin organogenesis and establish zebrafish as an experimentally accessible in vivo model for the study of Merkel cell biology.

developmental biology↗

Glia actively sculpt sensory neurons by controlled phagocytosis to tune animal behavior

Glia in the central nervous system engulf neuron fragments during synapse remodeling and recycling of photoreceptor outer-segments. Whether glia passively clear shed neuronal debris, or actively remove neuron fragments is unknown. How pruning of single-neuron endings impacts animal behavior is also unclear. Here we report that adult C. elegans AMsh glia engulf sensory endings of the AFD thermosensory neuron. Engulfment is regulated by temperature, AFDs sensory input, and tracks AFD activity. Phosphatidylserine (PS) flippase TAT-1/ATP8A, functions with glial PS-receptor PSR-1/PSR and PAT-2/-integrin to initiate engulfment. Glial CED-10/Rac1 GTPase, acting through a conserved GEF complex, executes phagocytosis using the actin-remodeler WSP-1/nWASp and the membrane-sealing factor EFF-1 fusogen. CED-10 levels determine engulfment rates, and engulfment-defective mutants exhibit altered AFD-ending shape and thermosensory behavior. Our findings reveal a molecular pathway underpinning glia-dependent phagocytosis in a peripheral sense-organ, and demonstrate that glia actively engulf neuron-fragments, with profound consequences on neuron shape and animal behavior.

neuroscience↗