Biology subjects

Faucz, F. R.

Publications and source records attributed to Faucz, F. R..

5 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↗

bioRxiv2024

Tendon-associated gene expression precedes osteogenesis in mid-palatal suture establishment

Orthodontic maxillary expansion relies on intrinsic mid-palatal suture mechanobiology to induce guided osteogenesis, yet establishment of the mid-palatal suture within the continuous secondary palate and causes of maxillary insufficiency remain poorly understood. In contrast, advances in cranial suture research hold promise to improve surgical repair of prematurely fused cranial sutures in craniosynostosis to potentially restore the obliterated signaling environment and ensure continual success of the intervention. We hypothesized that mid-palatal suture establishment is governed by shared principles with calvarial sutures and involves functional linkage between expanding primary ossification centres with the midline mesenchyme. We characterized establishment of the mid-palatal suture from late embryonic to early postnatal timepoints. Suture establishment was visualized using histological techniques and multimodal transcriptomics. We identified that mid-palatal suture formation depends on a spatiotemporally controlled signalling milieu in which tendon-associated genes play a significant role. We mapped relationships between extracellular matrix-encoding gene expression, tenocyte markers, and novel suture patency candidate genes. We identified similar expression patterns in FaceBase-deposited scRNA-seq datasets from cranial sutures. These findings demonstrate shared biological principles for suture establishment, providing further avenues for future development and understanding of maxillofacial interventions.

developmental biology↗

bioRxiv2023

Dkk2 interacts with Pax9 in palate mesenchyme to pattern and tune osteogenesis

Multiple genetic and environmental etiologies contribute to the pathogenesis of cleft palate, which constitutes the most common among the inherited disorders of the craniofacial complex. Insights into the molecular mechanisms regulating osteogenic differentiation and patterning in the palate during embryogenesis are limited and needed for the development of innovative diagnostics and cures. This study utilized the Pax9-/- mouse model with a consistent phenotype of cleft secondary palate to investigate the role of Pax9 in the process of palatal osteogenesis. While prior research had identified upregulation of Wnt pathway modulators Dkk1 and Dkk2 in Pax9-/- palate mesenchyme, limitations of spatial resolution and technology restricted a more robust analysis. Here, data from single-nucleus transcriptomics and chromatin accessibility assays validated by in situ highly multiplex targeted single-cell spatial profiling technology suggest a distinct relationship between Pax9+ and osteogenic populations. Loss of Pax9 results in spatially restricted osteogenic domains bounded by Dkk2, which normally interfaces with Pax9 in the mesenchyme. These results suggest that Pax9-dependent Wnt signaling modulators influence osteogenic programming during palate formation, potentially contributing to the observed cleft palate phenotype.

developmental biology↗

bioRxiv2023

Integrated spatiotemporal transcriptomic resolution of embryonic palate osteogenesis

The differentiation of osteoblasts and the subsequent formation of bone marks an important terminal phase in palate formation that leads to the separation of the oral and nasal cavities. While the developmental events that precede palatal osteogenesis are well explored, major gaps remain in our understanding of the molecular mechanisms that lead to the bony union of fusing palatal shelves. Herein, the timeline of osteogenic transcriptional programming is unveiled in the embryonic palate by way of integrated bulk, single-cell, and spatially resolved RNA-seq analyses. We define spatially restricted expression patterns of key marker genes, both regulatory and structural, that are differentially expressed during palatal fusion, including the identification of several novel genes (Deup1, Dynlrb2, Lrrc23) spatially restricted in expression to the palate, providing a relevant framework for future studies that identify new candidate genes for cleft palate anomalies in humans as well as the timing of mammalian embryonic palatal osteogenesis.

developmental biology↗

bioRxiv2022

Steroidogenic factor-1 lineage origin of skin lesions in Carney complex syndrome

Carney complex (CNC) is a rare familial multi-neoplastic syndrome predisposing to endocrine and non-endocrine tumors due to inactivating mutations of PRKAR1A leading to perturbations of the cAMP protein kinase A (PKA) signaling pathway. Skin lesions are the most common manifestation of CNC, including lentigines, blue nevi and cutaneous myxomas, in unusual locations such as oral and genital mucosa. Unlike endocrine disorders, the pathogenesis of skin lesions remains unexplained. Here, we show that embryonic invalidation of the Prkar1a gene in Steroidogenic Factor-1-expressing cells, leads to the development of familial skin pigmentation alterations reminiscent of those in patients. Immunohistological and molecular analyses coupled with genetic monitoring of recombinant cell lineages in mouse skin, suggest that familial lentiginosis and myxomas occurs in skin areas specifically enriched in dermal melanocytes. In lentigines and blue nevi-prone areas from mutant mice and patients, Prkar1a/PRKAR1A invalidation occurs in a subset of dermal fibroblasts capable of inducing, under the influence of PKA signaling, the production of pro-melanogenic EDN3 and HGF signals. Our model strongly suggests that the origin of the typical CNC cutaneous lesions is the result of non-cell-autonomous pro-melanogenic activity of a dermal fibroblast population sharing a community of origin with SF-1 lineage.

pathology↗