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Fogarty, N.

Publications and source records attributed to Fogarty, N..

4 recordsLinked to original sources

Impaired loading following denervation elicits dynamic, differential growth trajectories of musculoskeletal tissues

Physical forces dictate the function and maintenance of adult musculoskeletal tissues. Yet, the impact of biophysical cues on the growth and maturation of these tissues, especially dense connective tissues, remains unclear. Here, we investigated the effects of neonatal mechanical loading on early postnatal growth of the musculoskeletal tissues of the lower limb, with particular focus on the Achilles tendon. We performed sciatic nerve resection (SNR) on one-day-old mice to denervate the hamstrings and distal hindlimb muscles. Sciatic Nerve Resection resulted in severe and sustained alterations in gait, accompanied by an altered transcriptional landscape in distal musculoskeletal tissues, with marked reductions in bone and tendon growth and smaller, fibrotic hindlimb musculature. Sciatic nerve resection impaired cumulative growth in the Achilles tendon, shifting cell proliferation and matrix-driven growth trajectories and altering mechanotransduction gene programs toward inflammation and matrix catabolism with age. This work highlights the essential role of mechanical loading in driving mechanosignaling and postnatal growth trajectories in musculoskeletal tissues of the developing limb, with implications for overall musculoskeletal health in adulthood.

bioengineering↗

Evolutionary rewiring of the endomesoderm gene regulatory networks specify skeleton secreting cells in stony corals.

Stony corals are the eponymous keystone organisms for the most diverse marine ecosystems on earth: coral reefs. Despite their importance, little is known about the developmental genetic programs that drive their embryonic development and subsequent emergence of coral-specific traits. Like all developmental processes, coral development is governed by a series of genetic interactions collectively termed a gene regulatory network. Evolutionary changes in these gene regulatory networks are key sources of biological innovation, but how these networks operate in corals and how they have changed over time remains poorly understood. Here, we integrate chromatin profiling and transcriptomics to define the cis-regulatory architecture of early development in stony corals using the emerging model, Astrangia poculata. We find that key elements of the deeply conserved cnidarian endomesoderm gene regulatory network have been co-opted into a novel subnetwork that specifies secretory cells in corals. Using transgenic reporter assays, we found that a proximal cis-regulatory element of the endomesodermal gene Brachyury is sufficient to drive coral-specific expression patterns in the sea anemone Nematostella vectensis, demonstrating these elements as a key evolvable unit in stony corals. Collectively these findings establish a gene-regulatory framework for coral development and cell specification and suggest that evolutionary rewiring of ancestral developmental programs is a key driver in the evolution and diversification of stony corals.

developmental biology↗

Plantar flexor deficits following Achilles tendon rupture: a novel small animal dynamometer and detailed instructions

Plantar flexor functional deficits measured using joint dynamometry are associated with poor outcomes in patients following Achilles tendon rupture. In this study, we developed a small animal dynamometer to quantify functional deficits in a rat Achilles tendon rupture model. Like our reported plantar flexor deficits in patients recovering from Achilles tendon ruptures, we found in our small animal model functional deficits across the ankle range of motion, resulting in an average 34% less positive work being done compared to the uninjured contralateral limb. These functional deficits are similar to 38% less plantar flexor work done by patients who were treated non-surgically in our prior research. Further, these deficits were greater in plantar flexion than dorsiflexion, which agree with clinical complaints of limited function during tasks like jumping and hiking. These findings highlight the impact of muscle-tendon loading during early tendon healing on long-term plantar flexor function and serve as compelling evidence that our Sprague Dawley rat model of an Achilles tendon rupture recapitulates the human disease. We provide thorough documentation for other groups to build their own dynamometers, which can be modified to meet unique experimental criteria. SIGNIFIGANCEPreclinical models are critical tools for translating knowledge discovery to clinical decision making. We developed a low-cost and flexible joint dynamometer that quantifies joint function in small animals. Here, we used a rat model to test the implications of Achilles tendon ruptures not surgically repaired on plantar flexor function. We found that Achilles tendon ruptures in a rodent model closely resemble the functional deficits our group has observed in patients.

bioengineering↗

Genomic variants among threatened Acropora corals

Genomic sequence data for non-model organisms are increasingly available requiring the development of efficient and reproducible workflows. Here, we develop the first genomic resources and reproducible workflows for two threatened members of the reef-building coral genus Acropora. We generated genomic sequence data from multiple samples of the Caribbean A. cervicornis (staghorn coral) and A. palmata (elkhorn coral), and predicted millions of nucleotide variants among these two species and the Pacific A. digitifera. A subset of predicted nucleotide variants were verified using restriction length polymorphism assays and proved useful in distinguishing the two Caribbean Acroporids and the hybrid they form (\"A. prolifera\"). Nucleotide variants are freely available from the Galaxy server (usegalaxy.org), and can be analyzed there with computational tools and stored workflows that require only an internet browser. We describe these data and some of the analysis tools, concentrating on fixed differences between A. cervicornis and A. palmata. In particular, we found that fixed amino acid differences between these two species were enriched in proteins associated with development, cellular stress response and the hosts interactions with associated microbes, for instance in the Wnt pathway, ABC transporters and superoxide dismutase. Identified candidate genes may underlie functional differences in the way these threatened species respond to changing environments. Users can expand the presented analyses easily by adding genomic data from additional species as they become available.\n\nArticle SummaryWe provide the first comprehensive genomic resources for two threatened Caribbean reef-building corals in the genus Acropora. We identified genetic differences in key pathways and genes known to be important in the animals response to the environmental disturbances and larval development. We further provide a list of candidate loci for large scale genotyping of these species to gather intra- and interspecies differences between A. cervicornis and A. palmata across their geographic range. All analyses and workflows are made available and can be used as a resource to not only analyze these corals but other non-model organisms.

genomics↗