Biology subjects

Kamaraj, M.

Publications and source records attributed to Kamaraj, M..

4 recordsLinked to original sources

bioRxiv2026

FAM83H couples keratin organization to Notch signaling during epidermal morphogenesis

Keratin intermediate filaments are essential for epidermal integrity, yet how keratin organization is coupled to the cell fate signaling that coordinates keratinocyte differentiation during epidermal morphogenesis remains poorly understood. Here, we identify FAM83H as a previously unrecognized regulator that links keratin cytoskeletal organization to epidermal cell fate decisions. Using mouse models and a human 3D microphysiological epidermis model, we show that loss of FAM83H disrupts epidermal architecture by impairing basal keratinocyte differentiation, organization, and cell-cell adhesion. Single-cell transcriptomic analysis of 3D epidermal tissues identified Notch signaling as prominently associated with cell populations lost upon FAM83H depletion. Mechanistically, FAM83H localizes to cell-cell junctions, where it organizes keratin filaments and desmosome integrity. Loss of FAM83H disrupts a desmoplakin-keratin-Notch1 complex at junctions, impairing Notch1 proteolytic activation and proper keratinocyte differentiation. Together, our work identifies FAM83H as a key regulator of epidermal morphogenesis that couples keratin cytoskeletal architecture to Notch1 signaling, and positions keratin-associated proteins as active participants in the epithelial fate decisions that govern epidermal homeostasis.

cell biology↗

bioRxiv2026

StrataChip: a microphysiological system capturing dynamic keratinocyte fate and mechanical transitions during human epidermal morphogenesis

Epidermal development and homeostasis require precise coordination between keratinocyte differentiation and mechanics. Still, the mechanisms integrating these processes remain poorly understood in part due to limitations of existing experimental systems. Here, we introduce StrataChip, a tractable microphysiological system that enables dynamic, multimodal interrogation of human epidermal morphogenesis. The platform integrates a media perfused dermal tissue with human epidermal keratinocytes within a microfluidic device and supports rapid epidermal stratification following establishment of an air-liquid interface. High-resolution confocal imaging and single-cell RNA-sequencing demonstrate that the StrataChip recapitulates key architectural and molecular features of human epidermis, including distinct basal, spinous, and granular layers defined by canonical differentiation markers and adhesion molecule organization. Single-cell profiling reveals transcriptionally distinct basal and spinous subpopulations, including transitional states associated with suprabasal commitment. Live 3D imaging in situ captures keratinocyte morphodynamics including basal cell delamination and asymmetric division, linking dynamic cellular behaviors to defined differentiation fates and stratification. Altogether, StrataChip provides a robust platform for a dynamic and mechanistic interrogation of how gene regulation and cell mechanics are coupled during epidermal morphogenesis.

bioengineering↗

bioRxiv2025

Topical Delivery of 4-Aminopyridine Enhances Skin Regeneration in Burn Wounds

Burn wounds are a common traumatic injury that impair cellular function and hinder the healing process, often resulting in significant skin loss. While autologous skin grafting is considered the gold standard for treating burns, its widespread use is limited due to donor site morbidity and the requirement for large amounts of tissue. Traditional wound dressings and treatments often fail to ensure complete recovery. Being initially FDA-approved to treat multiple sclerosis, 4-aminopyridine (4-AP) has also been shown to accelerate burn wound closure by transforming keratinocytes and fibroblasts when administered systemically. However, prolonged systemic use of 4-AP can lead to significant side effects. In this study, we aimed to repurpose 4-AP for treating skin burn wounds by delivering it topically using a laponite-gelatin gel formulation. This method allows for non-invasive and localized drug delivery on burn wound site. We evaluated the physical properties of the 4-AP gel shear thinning behavior, drug release kinetics, biocompatibility, and functional wound closure using a scratch assay. Moreover, our in vivo experiments showed that the 4-AP loaded gel accelerates wound healing by enhancing re-epithelialization and hair follicle regeneration and promoting fibroblast to myofibroblast transformation, which supports extracellular matrix remodeling after skin burns. This novel application of the 4-AP gel could offer a promising alternative to current burn wound therapies, potentially leading to improved outcomes for burn patients.

bioengineering↗

bioRxiv2023

Dynamic fate map of hindbrain rhombomeres in zebrafish

Understanding of the morphogenetic processes that underlie the patterning of the vertebrate hindbrain requires establishment of rhombomere (r) cell lineages. Using long term in vivo two-photon imaging of zebrafish transgenic lines and automated image processing tools, we provide a method to reconstruct the r2-r6 lineage trees from the onset of gastrulation through early neurulation. We provide a dynamic fate map of hindbrain patterning at single-cell resolution. We show that rhombomere progenitor domains are aligned along the anteroposterior (AP) and dorsoventral (DV) axes as early as the shield stage. Rhombomere progenitor domains show a segmental organization, parallel to the blastoderm margin that predicts the future AP order of hindbrain. The DV organization of rhombomeres is set by the segregation of the progenitors along the DV axis of the embryo. Progenitors located at the dorsal/medial part of the blastoderm form the ventral domain of the rhombomeres while the lateral progenitors constitute the dorsal part. Our study sheds light on the clonal origin of individual rhombomeres, spatial and temporal patterns of cell division and migration of rhombomere progenitors throughout the early steps of hindbrain morphogenesis.

developmental biology↗