Biology subjects

Martin, K. J.

Publications and source records attributed to Martin, K. J..

7 recordsLinked to original sources

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↗

bioRxiv2024

The sensory shark: high-quality phenotypic, genomic and transcriptomic data for the small spotted catshark Scyliorhinus canicula reveal the molecular bases of sensory organ evolution in jawed vertebrates

Cartilaginous fishes (chimaeras and elasmobranchs -sharks, skates and rays) hold a key phylogenetic position to explore the origin and diversifications of jawed vertebrates. Here, we report and integrate reference genomic, transcriptomic and morphological data in the small-spotted catshark Scyliorhinus canicula to shed light on the evolution of sensory organs. We first characterise general aspects of the catshark genome, confirming the high conservation of genome organisation across cartilaginous fishes, and investigate population genomic signatures. Taking advantage of a dense sampling of transcriptomic data, we also identify gene signatures for all major organs, including chondrichthyan specializations, and evaluate expression diversifications between paralogs within major gene families involved in sensory functions. Finally, we combine these data with 3D synchrotron imaging and in situ gene expression analyses to explore chondrichthyan-specific traits and more general evolutionary trends of sensory systems. This approach brings to light, among others, novel markers of the ampullae of Lorenzini electro-sensory cells, a duplication hotspot for crystallin genes conserved in jawed vertebrates, and a new metazoan clade of the Transient-receptor potential (TRP) family. These resources and results, obtained in an experimentally tractable chondrichthyan model, open new avenues to integrate multiomics analyses for the study of elasmobranchs and jawed vertebrates.

evolutionary biology↗

bioRxiv2023

Analysis of a shark reveals ancient habenular asymmetries in gnathostomes and points to Wnt regulation as a driving force in their diversification

The origin of left-right asymmetries in the vertebrate habenula remains largely unknown. Using a transcriptomic approach, we show that in a cartilaginous fish, the catshark Scyliorhinus canicula, habenulae exhibit marked asymmetries both in their medial and their lateral component. Comparisons across gnathostomes suggest that asymmetries in the catshark lateral habenulae reflect an ancestral gnathostome trait, independently lost in tetrapods and neopterygians. Analysis of the mechanisms underlying their formation highlights an essential role of Wnt signaling. Wnt activity is submitted to a dynamic, asymmetric regulation during habenula development, with a Nodal dependent left repression at a stage when precursors for lateral habenulae have exited cell cycles. Pharmacological treatments during this time window reveal that Wnt signaling promotes lateral right neuronal identities in the right lateral habenula, while its repression by Nodal in the left one promotes lateral left neuronal identities. Based on comparisons with the zebrafish and the mouse, we propose that habenular asymmetry formation and diversification in gnathostomes involve the same developmental logic, relying on a conserved temporal regulation of neurogenesis, shaping neuronal identities on both sides, and its modification by a dynamic Wnt activity, right-restricted in the ancestral state and prone to variations in time and space during evolution.

developmental biology↗

bioRxiv2020

Integrating remote sensing and jurisdictional observation networks to improve the resolution of ecological management

The emergence of citizen science, passive sensors (e.g., trail cameras and acoustic monitoring), and satellite remote sensing have enabled biological data to be collected at unprecedented spatial and temporal scales. There is growing interest in networking these datastreams to expedite the collection and synthesis of environmental and biological data to improve broad-scale ecological monitoring, but there are no examples of such networks being developed to directly inform decision-making by managing agencies. Here, we present the implementation of one such jurisdictional observation network (JON), Snapshot Wisconsin (SW), that links satellite remote sensing (RS) with a volunteer-based trail camera network to generate new insights into wildlife distributions and improve their management by the state agency. SW relies on citizen scientists to deploy trail cameras across the state and classify images of wildlife. As of early 2020 SW comprises nearly 1800 volunteers hosting >2100 active cameras recording >37 million images across a sampling effort of >2000 combined trap-years at >3300 distinct camera locations. We use a set of case studies to demonstrate the potential power of a JON to monitor wildlife with unprecedented combinations of spatial, temporal, and biological resolution and extent. Specifically, we demonstrate that SW markedly improves the spatial and temporal resolution with which black bear distributions can be monitored or forecast, in turn improving the resolution of decision-making. Enhancing the biological resolution of monitoring (e.g., monitoring the distribution of species traits or behaviors) may provide new insights into population drivers, such as the connection between vegetation productivity and white-tailed deer foraging behaviors. Enhanced taxonomic extent provided by trail cameras and other passive sensor networks provide managers new information for a wide range of species and communities that are not otherwise monitored. Our cases further show that JONs synergize existing monitoring practices by serving as a complementary and independent line of evidence or as a tool to enhance the extent and precision of existing models through integrated modeling approaches. SW and other JONS are a powerful new tool for agencies to better achieve their missions and reshape the nature of environmental decision-making.

ecology↗

bioRxiv2020

A role for the autophagic receptor, SQSTM1/p62, in trafficking NF-kB/RelA to nucleolar aggresomes

Elevated NF-{kappa}B activity is a contributory factor in many haematological and solid malignancies. Nucleolar sequestration of NF-{kappa}B/RelA represses this elevated activity and mediates apoptosis of cancer cells. Here we set out to understand the mechanisms that control the nuclear/nucleolar distribution of RelA and other regulatory proteins, so that agents can be developed that specifically target these proteins to the organelle. We demonstrate that RelA accumulates in intra-nucleolar aggresomes in response to specific stresses. We also demonstrate that the autophagy receptor, SQSTM1/p62, accumulates alongside RelA in these nucleolar aggresomes. This accumulation is not a consequence of inhibited autophagy. Indeed, our data suggest nucleolar and autophagosomal accumulation of p62 are in active competition. We identify a conserved motif at the N-terminus of p62 that is essential for nucleoplasmic-to nucleolar transport of the protein. Furthermore, using a dominant negative mutant deleted for this nucleolar localisation signal (NoLS), we demonstrate a role for p62 in trafficking RelA and other aggresome-related proteins to nucleoli. Together, these data identify a novel role for p62 in trafficking nuclear proteins to nucleolar aggresomes under conditions of cell stress, thus maintaining nuclear proteostasis. They also provide invaluable information on the mechanisms that regulate the nuclear/nucleolar distribution of RelA that could be exploited for therapeutic purpose. SignificanceAberrant NF-{kappa}B activity drives many of the hallmarks of cancer and plays a key role in cancer progression. Nucleolar sequestration of NF-{kappa}B/RelA is one mechanism that switches off this activity and induces the death of cancer cells. Here we define a novel role for the autophagy receptor, SQSTM1/p62 in transport of nucleoplasmic NF-{kappa}B/RelA to nucleoli. Identification of this new trafficking mechanism opens up avenues for the development of a unique class of therapeutic agents that transport RelA and other cancer regulatory proteins to this organelle.

cell biology↗

bioRxiv2019

Seeing around corners: Cells create chemotactic gradients to solve mazes and respond to distant cues in complex environments.

Chemotaxis, in which cells steer using chemical gradients, drives fundamental biological processes like embryogenesis, metastasis and immune responses. Self-generated chemotaxis, where cells break down abundant attractants to create gradients, is an important but under-studied aspect of physiological navigation. Here we show that self-generated gradients allow cells to navigate arbitrarily complex paths and, remarkably, make accurate choices about pathways they have not yet encountered. This enables cells to solve microfluidic mazes, even with initially homogeneous environments and distant correct destinations. We combine computational models and experiments to understand how cells anticipate environmental features, and how decision accuracy is determined by path complexity, attractant diffusibility and cell speed. This permits mazes that are easy or hard for cells to resolve, despite similar appearances. Counterintuitively, slowly-diffusing attractants can generate a "mirage", making cells prefer dead ends over correct paths. In vivo environments resemble complex mazes, and only self-generated gradients realistically explain cell behaviour.

cell biology↗

bioRxiv2017

CYRI (FAM49) proteins are local inhibitors of Scar/WAVE induced lamellipodia that bind directly to active Rac1

Actin-based protrusions driving cell migration are reinforced through positive feedback, but it is unclear how the cell restricts the eventual size of a protrusion or limits positive signals to cause splitting or retraction. We have identified an evolutionarily conserved regulator of the protrusion machinery, which we name CYRI (CYFIP-related Rac interacting) protein. CYRI shows sequence similarity to the Scar/WAVE complex member CYFIP in a Domain of Unknown Function, DUF1394. CYRI binds specifically to activated Rac1 via a common motif shared with CYFIP, establishing DUF1394 as a new Rac1 binding domain. CYRI-depleted cells have broad, Scar/WAVE-enriched lamellipodia and enhanced Rac1 signaling. Conversely, CYRI overexpression suppresses spreading and dramatically sharpens protrusions into unproductive needles. CYRI proteins use dynamic inhibition of Scar/WAVE induced actin to focus positive protrusion signals and regulate pseudopod complexity. CYRI behaves like a \"local inhibitor\" predicted and described in widely accepted mathematical models, but not previously identified in living cells.

cell biology↗