Biology subjects

Marvel, M.

Publications and source records attributed to Marvel, M..

3 recordsLinked to original sources

bioRxiv2025

A novel transgenic reporter to study vertebrate epigenetics

Epigenetic reprogramming contributes to the generation of cellular diversity during vertebrate development but the mechanisms directing this are still not well understood. Large-scale genetic screens have been highly successful in identifying epigenetic regulatory genes in invertebrates such as worms and flies, but similar large-scale genetic screens to identify epigenetic regulators have not been carried out in vertebrates. Here we report a newly generated "EpiTag" zebrafish transgenic reporter line that permits easy cellular-level visualization of epigenetic silencing or activation in living animals during development, gametogenesis, and regeneration. We use the EpiTag reporter to carry out an F3 ENU mutagenesis screen for epigenetic silencing or activating mutants, identifying relevant vertebrate tissue-specific epigenetic regulatory genes including a new epigenetic model for metabolic dysfunction-associated fatty liver disease (MAFLD). The EpiTag reporter line represents a powerful new tool for genetic and experimental analysis of tissue-specific epigenetic gene regulation in vertebrates. One Sentence SummaryEpiTag transgenic zebrafish provide a powerful new tool for visualizing and studying epigenetic regulation in living vertebrate animals.

genomics↗

bioRxiv2025

Early epigenetic priming of regeneration studied with a novel transgenic epigenetic reporter

Tissue regeneration requires previously differentiated cells to regain developmental plasticity. However, the upstream mechanisms initiating this process remain poorly understood. Here, we leverage a novel "EpiTag" transgenic zebrafish reporter line that enables real-time visualization of epigenetic silencing and activation to identify and carry out a comprehensive multi-omics analysis of cells undergoing epigenetic reprogramming during caudal fin regeneration. EpiTag GFP expression is transiently activated in cells contributing to regeneration between 12 to 16 hours post amputation (hpa), preceding the expression of canonical blastema markers. Single-cell RNA-seq reveals that GFP+ cells are restricted to regeneration-competent lineages such as pre-osteoblasts, proliferating cells, and wound epithelium. Integrated bulk RNA-seq, time-course RNA-seq, ATAC-seq, and bisulfite-seq on FACS-isolated GFP+ cells uncovers an early gene expression module enriched for chromatin regulators and a late gene expression module enriched for morphogenesis genes. Chromatin accessibility and DNA methylation changes are strongly associated with these late-expressed genes, suggesting epigenetic priming. We identify a number of epigenetic factors upregulated in the early gene expression module and show that ruvbl1 and ruvbl2, components of ATP-dependent chromatin remodeling complexes, are required for proper regeneration in both adult fins and larval tails. Our results establish EpiTag transgenics as a powerful in vivo tool for studying epigenetic reprogramming and highlight early chromatin remodeling events that enable activation of regenerative gene expression programs.

genomics↗

bioRxiv2024

The axillary lymphoid organ - an external, experimentally accessible immune organ in the zebrafish

Lymph nodes and other secondary lymphoid organs play critical roles in immune surveillance and immune activation in mammals, but the deep internal locations of these organs make it challenging to image and study them in living animals. Here, we describe a previously uncharacterized external immune organ in the zebrafish ideally suited for studying immune cell dynamics in vivo, the axillary lymphoid organ (ALO). This small, translucent organ has an outer cortex teeming with immune cells, an inner medulla with a mesh-like network of fibroblastic reticular cells along which immune cells migrate, and a network of lymphatic vessels draining to a large adjacent lymph sac. Noninvasive high-resolution imaging of transgenically marked immune cells can be carried out in the lobes of living animals, and the ALO is readily accessible to external treatment. This newly discovered tissue provides a superb model for dynamic live imaging of immune cells and their interaction with pathogens and surrounding tissues, including blood and lymphatic vessels. TeaserA newly characterized external zebrafish lymphoid organ provides a powerful model for live imaging of immune cell dynamics

developmental biology↗