Biology subjects

Thiery, A. P.

Publications and source records attributed to Thiery, A. P..

5 recordsLinked to original sources

bioRxiv2026

Spatial Patterning of Otic Vesicles in Human Inner Ear Organoids

During development axial patterning of the otic vesicle sets up the blueprint for the adult inner ear. While human inner ear organoids recapitulate the initial steps of ear formation, whether and how vesicles are properly regionalised remains unknown. Here, we combine re-analysis of published single-cell transcriptomic datasets with 2D and 3D imaging to assess axial patterning in human stem-cell-derived otic vesicles using a new PAX2-reporter line. We find that the transcriptional signatures of individual cells do not conform to clearly defined regional characteristics, with some cells co-expressing conflicting regional markers, while markers that should be co-expressed are not. Some vesicles establish spatially segregated molecular domains. However, patterning is incomplete, stochastic, and restricted to a subset of vesicles. Within the same aggregates, patterned axes lack consistent orientation. Together, our findings point to incomplete segregation of transcriptional programs that are mutually exclusive in vivo and to the absence of morphogen gradients that are crucial for otic vesicle patterning. >One sentence summaryIn human inner ear organoids, otic vesicles show incomplete and disorganized regionalisation pointing to fundamental limits of self-organization, while suggesting new routes to increase cell complexity in vitro.

developmental biology↗

bioRxiv2025

Shark tooth regeneration: RNAseq reveals genes for unlimited dental renewal

Sharks are masters of tooth regeneration with a rapid and unlimited tooth supply. We present a comprehensive transcriptomic analysis across five distinct compartments from the embryonic shark mouth, capturing the full sequence of shark tooth development. Differential gene expression and gene regulatory network analyses reveal novel candidate markers upregulated within epithelial stem cells of the dental lamina. We show a potential role for this conserved regenerative network in the regulation of tooth production in sharks. Notably, we find the proto-oncogene mycn co-expressed with a definitive dental stem cell marker, sox2. Perturbation of mycn disrupts stem cell proliferation, underscoring its role in regulating dental stem cells in sharks. Our data showcase the power of transcriptome-based developmental approaches in the identification of predictive gene networks governing unlimited dental regeneration. The shark dental lamina provides an accessible system for the study of regeneration, offering exciting opportunities for investigating translational mechanisms of natural tooth renewal. TeaserSequencing dental stem cells in sharks reveals new genes necessary for lifelong tooth development.

developmental biology↗

bioRxiv2025

A single cell ATAC-seq atlas uncovers dynamic changes in chromatin accessibility during cell fate specification at the neural plate border

During development, dynamic changes in gene expression and chromatin architecture drive the transition from progenitors to specialised cell types. Here we use single cell ATAC sequencing (scATAC-seq) to investigate changes in chromatin accessibility as neural plate border cells segregate into neural, neural crest and placode cells. We developed a Nextflow pipeline, single cell Advanced Chromatin Exploration (scACE), which integrates scATAC-seq and scRNA-seq data to identify cell state specific accessibility profiles and groups of chromatin regions with coordinated dynamic behaviour, termed accessibility modules (AMs). We find that progenitors are characterised by broadly open chromatin, reflecting their broad potential to generate any ectodermal derivative. As development proceeds, cell-type-specific chromatin signatures are established. Inferring an enhancer-centric gene regulatory network, we predict Foxk2 as new regulator for placode specification and verify this prediction experimentally. Foxk2 target enhancers are open in placodal, but not any other ectodermal cells. This finding suggests that on a regulatory level, cells can use different strategies to control fate choice: differential accessibility of enhancers and broad accessibility controlled by differentially expressed transcription factors.

developmental biology↗

bioRxiv2021

An ancient dental signalling centre supports homology of an enamel knot in sharks

Development of tooth cusps is regulated by the enamel knot signalling centre. Fgf signalling regulates differential proliferation between the enamel knot and adjacent dental epithelia during tooth development, leading to formation of the dental cusp. The presence of an enamel knot in non-mammalian vertebrates is debated given differences in signalling. Here we show the conservation and restriction of fgf10 and fgf3 to the sites of future dental cusps in the shark (Scyliorhinus canicula), whilst also highlighting striking differences between the shark and mouse. We reveal shifts in tooth size, shape and cusp number following small molecule perturbations of canonical Wnt signalling. Resulting tooth phenotypes mirror observed effects in mammals, where canonical Wnt has been implicated as an upstream regulator of enamel knot signalling. In silico modelling of shark dental morphogenesis demonstrates how subtle changes in activatory and inhibitory signals can alter tooth shape, resembling phenotypes observed following experimental Wnt perturbation. Our results support the functional conservation of an enamel knot-like signalling centre throughout vertebrates and suggest that varied tooth types from sharks to mammals follow a similar developmental bauplan. Lineage-specific differences in signalling are not sufficient in refuting homology of this signalling centre, which is likely older than teeth themselves.

developmental biology↗

bioRxiv2018

Evolution and developmental diversity of skin spines in pufferfish

Teleost fishes develop a huge variety of skin ornaments. How these diverse skin structures develop in fishes is unknown. The teleost fish order Tetraodontiformes includes some of the most unusual fishes such as the ocean sunfish, triggerfish and pufferfish, and they all can develop a vast assortment of scale derivatives that cover their bodies. Pufferfish have some of the most extreme scale derivatives, dermal spines, which are erected during their characteristic puffing behavior. Here we show that pufferfish spines develop through conserved gene interactions essential for other vertebrate skin appendage formation, like hair and feathers. However, pufferfish spines form without EDA (ectodysplasin), an essential molecule for the development of most vertebrate skin appendages. Modifying signaling pathways lead to loss or reduction of spine coverage in pufferfish, suggesting a mechanism for skin appendage diversification. We suggest that pufferfish skin spines evolved from a basic teleost scale-type through derived gene network modification in Tetraodontiformes.

developmental biology↗