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Rosa, J. B.

Publications and source records attributed to Rosa, J. B..

3 recordsLinked to original sources

Mucus cell and ionocyte precursors migrate between epithelial cells to disperse through the zebrafish epidermis

Mucus-secreting cells and ionocytes play critical roles in many organs. Both cell types are usually distributed as scattered, solitary cells within an epithelium, a pattern presumably optimal for their function. To investigate how they attain their dispersed distributions, we imaged mucus cell and ionocyte precursors in the epidermis of developing zebrafish. Previous reports found that precursors of both cell types are first detected in the ventral epidermis (covering the yolk) before spreading dorsally, but the mechanism driving this progression was unknown. Photoconverting basal epidermal cells in the ventral embryo revealed that some cells actively migrate away from this area to populate the rest of the epidermis. These cells lose their basal cell identity when they start migrating and begin expressing markers of mature mucus cells or ionocytes during migration. These cells travel entirely between the two epithelial layers of the epidermis, occasionally pause migration to divide, and repel one another through contact inhibition of locomotion, behaviors that likely aid in their dispersal. After migrating for about a day, mucus cell and ionocyte precursors intercalate into the superficial epithelial layer of the epidermis, where they complete differentiation. These observations reveal how mucus cells and ionocytes achieve their scattered distributions in the zebrafish epidermis, suggesting that similar processes promote their distribution in other mucosal organs.

developmental biology↗

Reverse electron transfer at mitochondrial complex I restrains dopaminergic neuron activity to promote early-life sleep in Drosophila

Sleep is especially abundant during early life, yet the cellular mechanisms that maintain elevated juvenile sleep drive remain poorly understood. To identify cell-intrinsic regulators of juvenile sleep, we profiled gene expression in Drosophila dopaminergic neurons (DANs) at different ages and performed a targeted RNAi screen of genes with enriched juvenile expression. We found that the magnitude of mitochondrial complex I (MCI) disruption produced strikingly distinct physiological outcomes. Severe MCI loss-of-function caused profound mitochondrial dysfunction, reduced dopaminergic activity, and locomotor impairment. In contrast, partial MCI inhibition left overall mitochondrial function intact but instead reduced sleep, with disproportionately strong effects on juvenile sleep fragmentation and depth, consistent with a gain of dopaminergic signaling. Multiple genetic manipulations that deplete the reduced coenzyme Q pool (CoQH2) converged on a phenotype of increased dopaminergic activity and wakefulness, indicating that coenzyme Q redox balance itself regulates dopaminergic output. These findings support a model in which CoQH2-driven reverse electron transfer (RET) at MCI restrains dopaminergic arousal. By dissociating mitochondrial redox signaling from catastrophic mitochondrial failure, our work identifies a physiological role for coenzyme Q-dependent signaling in the regulation of neural activity and behavioral state. More broadly, these findings suggest that sleep phenotypes may serve as sensitive indicators of emerging mitochondrial dysfunction and reveal a potential link between the regulation of early-life sleep and later dopaminergic vulnerability.

neuroscience↗

Sensory axons induce epithelial lipid microdomain remodeling and determine the distribution of junctions in the epidermis

Epithelial cell properties are determined by the polarized distribution of membrane lipids, the cytoskeleton, and adhesive junctions. Epithelia are often profusely innervated, but little work has addressed how contact with neurites affects the polarized organization of epithelial components. In previous work, we found that basal keratinocytes in the larval zebrafish epidermis wrap around axons to enclose them in ensheathment channels sealed by autotypic cell junctions. In this study, we used live imaging to characterize how sensory axons remodel cell membranes, the actin cytoskeleton, and adhesive junctions in basal keratinocytes. At the apical surface of basal keratinocytes, axons promoted the formation of lipid microdomains quantitatively enriched in reporters for PI(4,5)P2 and liquid-ordered (Lo) membranes. Lipid microdomains supported the formation of cadherin-enriched F-actin protrusions, which wrapped around axons, likely initiating the formation of ensheathment channels. Lo reporters, but not reporters of liquid-disordered (Ld) membranes, became progressively enriched at axon-associated membrane domains as autotypic junctions matured at ensheathment channels. In the absence of axons, cadherin-enriched lipid microdomains still formed on basal cell membranes, but were not organized into the contiguous domains normally associated with axons. Instead, these isolated domains formed ectopic heterotypic junctions with overlying periderm cells, a distinct epithelial cell type in the epidermis. Thus, axons inhibit the formation of epithelial heterotypic junctions by recruiting cadherin-rich lipid microdomains to form autotypic junctions at ensheathment channels. These findings demonstrate that sensory nerve endings dramatically remodel polarized epithelial components and regulate the adhesive properties of the epidermis.

cell biology↗