Selected Grantee Publications
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- 29 results found
- Aquatic Vertebrate Models
- 2024
- 2021
Stat3 Mediates Fyn Kinase-Driven Dopaminergic Neurodegeneration and Microglia Activation
Siddiqui et al., Disease Models & Mechanisms. 2024.
https://pubmed.ncbi.nlm.nih.gov/39641161
The FYN gene is a risk locus for Alzheimer’s disease and several other neurodegenerative disorders. FYN encodes Fyn kinase, and previous studies have shown that Fyn signaling in dopaminergic neurons and microglia plays a role during neurodegeneration. This study investigated Fyn signaling using zebrafish that express a constitutively active Fyn Y531F mutant in neural cells. Activated neural Fyn signaling in the mutant animals resulted in dopaminergic neuron loss and induced inflammatory cytokine expression when compared with controls. Transcriptomic and chemical inhibition analyses revealed that Fyn-driven changes were dependent on the Stat3 and NF-κB signaling pathways, which work synergistically to activate neuronal inflammation and degeneration. This study provides insight into the mechanisms underlying neurodegeneration, identifying Stat3 as a novel effector of Fyn signaling and a potential translational target. Supported by ORIP (R24OD020166).
Temperature-Dependent Alterations in the Proteome of the Emergent Fish Pathogen Edwardsiella piscicida
Jacobsen et al., Journal of Fish Diseases. 2024.
https://pubmed.ncbi.nlm.nih.gov/39304982
Reported outbreaks of Edwardsiella piscicida, a bacterial pathogen among cultured and wild fish, have been steadily increasing over the past decade in tandem with climate change–mediated increases in water temperatures. The capacity for this increasingly prevalent fish pathogen to infect and cause disease in mammals is important to understand. Researchers examined the role of temperature on the virulence of E. piscicida to understand its pathogenesis in the context of climate warming trends and better understand its zoonotic potential. Findings revealed downregulation of virulence-related proteins, such as flagellar and Type VI secretion system proteins, at colder temperatures. These findings highlight the potential environmental factors influencing the pathogen’s threat to aquaculture and public health. Supported by ORIP (S10OD026918, T32OD011147).
A New Atlas to Study Embryonic Cell Types in Xenopus
Petrova et al., Developmental Biology. 2024.
https://pubmed.ncbi.nlm.nih.gov/38614285
Petrova et al. have designed a new single-cell atlas for developmental stages in Xenopus tropicalis that encompasses gastrulation, neurulation, and early tail bud. Compared to its predecessors, the new atlas enhances gene mapping, read counts, and gene/cell-type nomenclature. The atlas also leverages the latest X. tropicalis genome version to maintain consistency with previous cell-type annotations while rectifying prior nomenclature issues. The new resource emphasizes previously unexplored germ-cell populations in which novel transcription onset features have been uncovered. Finally, the new atlas offers interactive exploration through a user-friendly web portal and allows users to download complete data sets. Supported by ORIP (R24OD031956).
Gap-Junction-Mediated Bioelectric Signaling Required for Slow Muscle Development and Function in Zebrafish
Lukowicz-Bedford et al., Current Biology. 2024.
https://pubmed.ncbi.nlm.nih.gov/38936363
Using the neuromuscular system of embryonic zebrafish as a model, Lukowicz-Bedford et al. have identified a protein that is responsible for controlling bioelectric signaling in slow muscle development and function. Bioelectric signaling is a form of intercellular communication that has emerged as a key regulator of animal development. These signals can be mediated by gap junction channels—fast, direct pathways between cells for the movement of ions and other small molecules—that are formed in vertebrates by a highly conserved transmembrane protein family called connexins. However, the connexin gene family is large and complex, making it challenging to identify specific connexins that create channels within developing and mature tissues. This work reveals a molecular basis for gap-junction communication among developing muscle cells and shows how disruptions to bioelectric signaling in the neuromuscular system may contribute to developmental myopathies. Supported by ORIP (R24OD026591), NINDS, and NIGMS.
Validity of Xiphophorus Fish as Models for Human Disease
Schartl and Lu, Disease Models and Mechanisms. 2024.
https://pubmed.ncbi.nlm.nih.gov/38299666/
Xiphophorus is the one of the oldest animal systems for studying melanoma. In this article, the authors summarize current Xiphophorus models for other human diseases. They review how Xiphophorus fishes and their interspecies hybrids can be used for studying human diseases and highlight research opportunities enabled by these unique models (both established and emerging). They identified several emerging Xiphophorus models, including for albinism, micromelanophore pigmentation, fin regeneration, and diet-induced obesity. The research on cancer and reproductive maturation discussed in this review substantiates the value of Xiphophorus as a model for human disease throughout all three phases of validation—face, construct, and predictive—and continues to provide important scientific insights. Supported by ORIP (R24OD031467, R21OD031910) and NCI.
Injury-Induced Cooperation of InhibinβA and JunB is Essential for Cell Proliferation in Xenopus Tadpole Tail Regeneration
Nakamura et al., Scientific Reports. 2024.
https://pubmed.ncbi.nlm.nih.gov/38355764/
Certain animal species (e.g., amphibians) that can regenerate lost tissues and limbs after injury offer potential for applications in regenerative medicine. Cell proliferation is essential for the reconstruction of injured tissue, but the molecular mechanisms that regulate the transition from wound healing to regenerative cell proliferation remain unclear. Using Xenopus tropicalis, investigators examined the effects of injury on the expression of inhibin subunit beta A (inhba) and junB proto-oncogene (junb). Their findings shed light on the mechanisms underlying injury-induced cell proliferation in regenerative animals. Supported by ORIP (P40OD010997, R24OD030008).
Establishment of a Practical Sperm Cryopreservation Pathway for the Axolotl (Ambystoma mexicanum): A Community-Level Approach to Germplasm Repository Development
Coxe et al., Animals (Basel). 2024.
https://pubmed.ncbi.nlm.nih.gov/38254376/
The axolotl (Ambystoma mexicanum) is an important biomedical research model for organ regeneration, but housing and maintaining live animals is expensive and risky as new transgenic lines are developed. The authors report an initial practical pathway for sperm cryopreservation to support germplasm repository development. They assembled a pathway through the investigation of axolotl sperm collection by stripping, refrigerated storage in various osmotic pressures, cryopreservation in various cryoprotectants, and in vitro fertilization using thawed sperm. This work is the first report of successful production of axolotl offspring with cryopreserved sperm and provides a general framework for pathway development to establish Ambystoma germplasm repositories for future research and applications. Supported by ORIP (R24OD010441, R24OD028443, P40OD019794).
Conduction-Dominated Cryomesh for Organism Vitrification
Guo et al., Advanced Science. 2024.
https://pubmed.ncbi.nlm.nih.gov/38018294/
Vitrification-based cryopreservation via cryomesh is a promising approach for maintaining biodiversity, health care, and sustainable food production via long-term preservation of biological systems. Here, researchers conducted a series of experiments aimed at optimizing the cooling and rewarming rates of cryomesh to increase the viability of various cryopreserved biosystems. They found that vitrification was significantly improved by increasing thermal conductivity, reducing mesh wire diameter and pore size, and minimizing the nitrogen vapor barrier of the conduction-dominated cryomesh. Cooling rates increased twofold to tenfold in a variety of biosystems. The conduction-dominated cryomesh improved the cryopreservation outcomes of coral larvae, Drosophila embryos, and zebrafish embryos by vitrification. These findings suggest that the conduction-dominated cryomesh can improve vitrification in such biosystems for biorepositories, agriculture and aquaculture, and research. Supported by ORIP (R24OD028444, R21OD028758, R24OD034063, R21OD028214), NIDDK, and NIGMS.
HDAC Inhibitor Titration of Transcription and Axolotl Tail Regeneration
Voss et al., Frontiers in Cell and Development Biology. 2021.
https://pubmed.ncbi.nlm.nih.gov/35036404/
New patterns of gene expression are enacted and regulated during tissue regeneration. Romidepsin, an FDA-approved HDAC inhibitor, potently blocks axolotl embryo tail regeneration by altering initial transcriptional responses to injury. Regeneration inhibitory concentrations of romidepsin increased and decreased the expression of key genes. Single-nuclei RNA sequencing at 6 HPA illustrated that key genes were altered by romidepsin in the same direction across multiple cell types. These results implicate HDAC activity as a transcriptional mechanism that operates across cell types to regulate the alternative expression of genes that associate with regenerative success versus failure outcomes. Supported by ORIP (P40OD019794, R24OD010435, R24OD021479), NICHD, and NIGMS.
Precise Visuomotor Transformations Underlying Collective Behavior in Larval Zebrafish
Harpaz et al., Nature Communications. 2021.
https://www.nature.com/articles/s41467-021-26748-0
Sensory signals from neighbors, analyzed in the visuomotor stream of animals, is poorly understood. The authors studied aggregation behavior in larval zebrafish and found that over development larvae transition from over dispersed groups to tight shoals. Young larvae turn away from virtual neighbors by integrating and averaging retina-wide visual occupancy within each eye, and by using a winner-take-all strategy for binocular integration. Observed algorithms accurately predict group structure over development. These findings allow testable predictions regarding the neuronal circuits underlying collective behavior in zebrafish. Supported by ORIP (R43OD024879, R44OD024879) and NINDS.