19th IZFC Meeting Report
By Yevgenya Grinblat and Brant Weinstein
The 19th International Zebrafish Conference, organized by the International Zebrafish Society, returned to Madison, WI in July. University of Wisconsin-Madison has hosted IZFC several times since 2002, and is home to a thriving zebrafish research community with 10 research labs working primarily or solely in zebrafish. This year, 583 zebrafish researchers from 21 countries across the world came together at the Memorial Union, along with 57 virtual attendees, to share cutting-edge research advances, showcasing the enduring power of zebrafish as a model organism for addressing both basic and translational biological questions in developmental biology, regenerative biology, and disease modeling.
The complementarity of basic and translational research was illustrated beautifully by the keynote lectures. In the opening keynote, Dr. L. Mahadevan (Harvard University) told us how his group combines wet-lab experiments and mathematical modeling to ask two fundamental questions in developmental evolutionary biology: what makes us the same – and what makes us different. The answers lie in quantitative differences in the processes of gastrulation, gut elongation, and segmentation. In the second keynote, Dr. Hanna Mikkola (UCLA) described how her team applies stem cell technology to understand the development of human hematopoietic stem cells and how it is applied to understanding and curing cancer.
Two award lectures were presented, one by Corinne Houart (King’s College London), who received the Christiane Nüsslein-Volhard Award, and one by the 11 past and present MBL Zebrafish Course Directors, who were recognized with the George Streisinger Award for 25 years of training innovation and community building in zebrafish research.
Scientists at all career levels presented their research in six plenary sessions, 11 concurrent sessions, and 3 poster sessions (Public Agenda). Below we highlight just a small sampling of the many exciting presentations, with an emphasis on early-career scientists and a few items of broad community interest. We encourage you to review the full agenda here. Abstracts and talk recordings are available with in-person or online registration until October 13.
SEEING IS BELIEVING: The extraordinary power of live imaging was on full display throughout the meeting.
Heather Barber from Sarah Kucenas’ lab (University of Virginia ) shared her PhD research using live imaging of transgenic zebrafish larvae to study glial cells in the optic tectum during a critical period of visual system development. She showed that the radial astroglia spanning the optic tectum surround and hold apoptotic neurons in large spherical compartments, then later transfer the debris to phagocytic microglia. Discoveries like these compartments, which Barber calls “scyllate heads” after a monster in Homer’s Odyssey, reveal how useful zebrafish are for finding transient phenomena that can only be captured with live imaging. She hopes that her work will inspire others to investigate how cells interact in unconventional ways during phagocytosis and other complex biological processes (a preprint on this work is available at doi.org/10.1101/2025.03.14.643334).
CAPTION: Confocal image from the brain of a 3 dpf Tg(sox10:eos) zebrafish larvae (anterior to the top). The labeled cells seen throughout the image are oligodendrocyte lineage cells. The Kucenas Lab studies cellular and molecular mechanisms driving glial development, including how these cells migrate, interact, tile, clear cellular debris, and myelinate axons.
Pui-Ying Lam (Medical College of Wisconsin) studies regeneration in the adult CNS in her lab, using an alternative fish model, Danionella cerebrum. This close relative of the zebrafish is approximately 27 times smaller in volume than the adult zebrafish, is transparent as an adult and naturally lacks the dorsal skull cap. These properties, together with conservation of regulatory sequences, allow generation of transgenic cell-labeling lines and live imaging of the brain and other tissues using light microscopy —even in adult animals. See https://journals.biologists.com/dmm/article/15/12/dmm049753/286133/Longitudinal-in-vivo-imaging-of-adult-Danionella for recent work from the Lam lab.
CAPTION: The adult D. cerebrum is approximately 27 times smaller in volume than the adult zebrafish.
Arndt Siekmann (University of Pennsylvania) presented work from his lab showing that adaptive changes in endothelial cell morphologies can drive blood vessel diameter changes, thereby controlling blood flow patterns. They identified an endothelial cell population that they named sphincter endothelial cells. These cells are present at arterial branch points and display unique morphologies and gene expression patterns. They further showed that mutations in endoglin, known to cause arteriovenous malformations, affect sphincter cell formation, thereby increasing flow into arterial side branches. The work, recently published in Diwan et al. (2024) shows that proper blood flow distribution within the arterial network relies on specialized endothelial cells.
Sofia DeOliviera (Albert Einstein College of Medicine) discussed her lab’s studies of neutrophil dynamics in polytraumatic injury. Using transgenic zebrafish larvae with fluorescently tagged neutrophils and whole-animal imaging, the lab tracked cells across multiple lineages following simultaneous (polytrauma) or single injuries. These analyses uncovered a triage mechanism in polytrauma response: neutrophils prioritize injuries in complex organs (liver, spinal cord) where neutrophil response peaks 2-4 hours post-injury, over skin, where it peaks 10-12 hours post-injury. Remarkably, all wounds display similar recruitment kinetics in single-injury settings, with the response peaking 4–6 h post-injury. Time-resolved reconstructions of cell shape and tracks (up to 18 h) yielded quantitative behavioral descriptors that were integrated into high-dimensional behavioral landscapes across injury sites. This analysis revealed that polytrauma not only alters recruitment kinetics, eliciting an exaggerated systemic response, but also produces distinct neutrophil behavioral signatures compared with single-injury counterparts, suggesting that polytrauma induces specific neutrophil subpopulations. Diet-induced systemic chronic inflammation disrupts this prioritization, blunting responses in complex organs and diverting cells toward skin. Finally, a sepsis-like LPS challenge 24 hours after polytrauma reduced survival from 93% to 45%, mirroring the clinical vulnerability of this high-risk group. These findings establish zebrafish as a powerful model for discovering systemic rules of neutrophil immune triage and organ/tissue regeneration after polytrauma under normal and metabolic syndrome conditions, and provide a scalable platform for whole-animal drug discovery to improve immune function, survival, and outcomes.
THE POWER OF GENETICS: The conference provided strong evidence of the continuing increase in genomic tools available for zebrafish research. New technologies for precise manipulation of the zebrafish genome are growing ever more sophisticated with optimization of HDR-driven knock-in, base editing and prime editing methods. Presentations on just a few of these tools are described below.
Shawn Burgess (National Human Genome Research Institute, NIH) described the recent release of two new zebrafish “telomere-to-telomere” reference genomes, GRCz12tu (GenBank #: GCA_049306965.1) and GRCz12ab (GenBank#: GCA_052040795.1). GRCz12tu was sequenced from a heatshock induced clone from the TU strain, while GRCz12ab was sequenced from the inbred AB line (M-AB) generated at the national Institute of Genetics in Mishima (https://www.nature.com/articles/s41598-024-57699-3 ). GRCz12tu has already been annotated by the RefSeq team and the annotations can be used in the UCSC Genome browser accessible through the Genome Archive, GenArk (https://genome.ucsc.edu/cgi-bin/hgTracks?db=hub_6654484_GCF_049306965.1). The new RefSeq annotations for GRCz12tu incorporated large new Iso-Seq and CAGE cDNA data which has greatly increased the number of transcript isoforms (+68%) and lncRNAs (+47%). RefSeq has put GRCz12ab into its annotation pipeline and Ensembl has also entered both assemblies into its gene annotation pipeline. All annotations are expected to be complete by the end of the year.
Steve Ekker (University of Texas in Austin) reported on his lab’s studies of mitochondria, a critical organelle essential for diverse critical functions from energy production to signaling. The mitochondrial genome represents one of the most highly conserved known stretches of vertebrate DNA, with all 37 genes found in the same order from zebrafish to humans. The FUSX TBE system https://www.biorxiv.org/content/10.1101/2021.05.18.444740v1.full enables editing zebrafish mitochondrial DNA through nucleotide base editing in this highly conserved circular genome. The lab also developed a refined noninvasive genotyping protocol to enable the rapid assessment of either mitochondrial or nuclear DNA, a critical need for these dynamic models bioRxiv 2025.04.30.651585. To date, 19 different zebrafish lines with high heteroplasmy have been generated, including 12 protein-encoding and seven RNA mitochondrial loci. These edits are stable through the germline and represent an advanced animal model for the study of mitochondrial science and understanding the fundamentals of mtDNA-based disease
A number of new tools for conditional expression or depletion of genes or gene products in the zebrafish were also described at the conference.
Benjamin Martin (Stony Brook University) described his labs’ work on implementing the auxin inducible degron (AID) system for conditional depletion of proteins in the zebrafish. He described testing variants of the system to optimize for rapid protein degradation and used these to test the role of the Sox2 transcription factor during midline progenitor cell development. This was achieved through heat-shock induced expression of AID-tagged Sox2, followed by timed degradation of the exogenous Sox2. He finished by describing new transgenic Tir1 (the plant F-box protein required to degrade AID tagged proteins in the presence of auxin) driver lines his lab has made, as well as AID-tagged endogenous transcription factor lines they generated to demonstrate the ability to degrade endogenous proteins with this system. A preprint describing the testing of AID system variants, and the use of AID-tagged Sox2 to better understand its role in midline progenitor development, can be found here: https://www.biorxiv.org/content/10.1101/2025.01.16.633481v2
Hyunju Ro (Chungnam National University in Daejon, Korea) described newly engineered QF/QUAS-based gene-switch tools to facilitate this promising alternative to the more commonly used GAL4/UAS system. By incorporating modifications that improve expression strength, reduce background activity, and enhance temporal control, these new tools enable more precise regulation of transgene expression in vivo, providing an expanded toolkit for the zebrafish community. Further details on these new tools were recently published in Communications Biology (Hong et al., 2021. https://www.nature.com/articles/s42003-021-02923-3) and Molecular Therapy – Methods & Clinical Development (Hong et al., 2024, https://linkinghub.elsevier.com/retrieve/pii/S2329-0501(24)00018-4).The lab is currently developing a novel dual-gene switch that will allow independent activation of two discrete genes in spatiotemporal patterns in both zebrafish and mammalian cells.
HUMAN DISEASE: As a direct result of advances in imaging and genetic technology, the zebrafish is becoming even more effective for modeling human disease and for drug discovery.
Nicholas Haghani (Megan Dennis’ lab, University of California Davis) described zebrafish knockout models of 18 candidate genes implicated in autism with disproportionate megalencephaly (ASD-DM). Mosaic CRISPant knockout larvae for 11 out of 18 candidate orthologs exhibited significantly altered morphometric features serving as proxies for brain size. Follow-up characterization at single-cell resolution of a knockout model for the high-confidence ASD-DM gene, chd8, reveals a delayed increase in cycling midbrain progenitor cells, also observed in published mouse and cerebral organoid models with brain enlargement. A recent publication on exploring autism with disproportionate megalencephaly in zebrafish models can be found here https://doi.org/10.1002/aur.3314
Summer Thyme ( UMass Chan Medical School) presented her lab’s progress on modeling Down’s syndrome-associated neurodevelopmental defects using zebrafish stable overexpression lines and measurements of whole brain activity and structure. Surprisingly, only one of 16 candidate genes produced detectable phenotypes, notably causing cerebellar reduction and increased expression of astrocyte-like cell markers, both of which are consistent with mouse models of Down syndrome. Looking toward therapeutic applications, Dr. Thyme also described two projects nearing completion: a screen of nearly 2,000 molecules for neurodevelopmental modulators and a novel computational drug discovery method that uses zebrafish as a testing platform for predicted compounds. Methods similar to these unpublished findings are described in this recent publication https://www.pnas.org/doi/abs/10.1073/pnas.2402557122
Ankit Sabharwal (University of Texas at Austin) reported on his lab’s progress in modeling mitochondrial disorders in zebrafish. Using the recently developed FusXTBE technology, the lab has established zebrafish models to recapitulate human mtDNA disorders https://www.biorxiv.org/content/10.1101/2021.05.18.444740v1.full. They have explored germline transmission dynamics and systemic consequences of near-complete (>80% heteroplasmy) of the mt-tl1 mutation. mt-tl1 mutants exhibited impaired mitochondrial bioenergetics and altered transcriptomic signatures. Intriguingly, differential segregation patterns across generations correlated with distinct transcriptomic profiles and hearing impairments analogous to clinical mitochondrial disorder. Additionally, they have established a novel mt-nd5 m.13311C>T mutant, achieving stable heteroplasmy levels between 40-70%. This mutant line exhibited reduced swimming activity, diminished Complex I enzyme activity, elevated lactate levels, increased oxidative stress markers, and altered mitochondrial metabolic fluxes indicative of Complex I deficiency. Collectively, these zebrafish avatars offer potential to be used as platforms to dissect mitochondrial pathophysiology in vivo, significantly advancing mechanistic understanding and targeted therapeutic strategies for mitochondrial diseases.
Hyun Min Jung (University Illinois, Chicago) presented work from his lab on how the microRNA miR-204 regulates lymphatic vessel remodeling and edema clearance in zebrafish. Intravital imaging revealed that miR-204 enhances lymphangiogenesis and interstitial fluid drainage, while RNA-seq identified LYVE1 as a key transcriptional target of this microRNA. Functional studies showed that mosaic miR-204 overexpression suppresses lyve1b reporter activity, and lyve1 mutants displayed improved edema resolution. Together, these findings establish a critical role for miR-204–Lyve1 balance in coordinating lymphatic remodeling during tissue recovery. This work, recently published in Scientific Reports (https://www.nature.com/articles/s41598-025-92970-1), opens potential therapeutic avenues for targeting edema and lymphatic-related disorders.
CAPTION: Confocal image showing blood (magenta) and lymphatic (green) vessels in the craniofacial region of a 9 dpf Tg(mrc1a:eGFP; kdrl:mCherry) larva after recovery from osmotic stress–induced edema. The Jung lab is interested in understanding how lymphatic vessels develop and function.
Keir Balla (Chan Zuckerberg Biohub, San Francisco) presented work on two large-scale efforts involving virus infection discovery and whole body immunology. They have constructed a pipeline that processes all publicly available zebrafish RNA-sequencing data in the Sequence Read Archive to quantify gene expression and all non-zebrafish transcript abundances, including diverse newly described viruses. Results from this work are intended to be a discovery engine for the community and they are producing portals and tools to facilitate access through ZFIN. In the second portion of his talk, Keir introduced new tools for profiling the entire immune system at the organismal scale with imaging, and advanced definitions of immune cell types based on shape and dynamic behaviors in addition to molecular profiles.
CAPTION: The Balla lab has generated transgenic zebrafish expressing mCherry in all immune cells and used a custom light sheet microscope to image the entire immune system for more than 24 hours in an 8 day old animal. They have also built models for cell segmentation and tracking throughout the body to quantify cell shapes and behaviors for decoding cell types and states from images.
Wilson Clements (St. Jude’s Children’s Research Hospital) presented data implicating enzymes used for sequential post-translational modification, structuring, and maturation of collagen in specification of hematopoietic stem cells during development. This work suggests the structural nature of stem cell niches contributes to their ability to direct cell fate outcomes.
Catherine Brown, a graduate student in the Farber lab (John Hopkins University) reported the results of her collaborative work with graduate student Michelle Biederman. The team applied single nucleus RNA-sequencing (snRNA-seq) to describe the transcriptional response of larval zebrafish to a lipid rich meal. To their knowledge, this is the first vertebrate snRNA-seq atlas characterizing how an entire organism responds to a metabolic stimulus over time (4h). Surprisingly, 650 unique genes were differentially expressed in 74 cell types within 15 minutes of feeding. Cat also performed snRNA-seq on fish lacking creb3l3, a poorly understood regulator of lipid-responsive gene expression. Combining these datasets will elucidate the complex cell-type specific transcriptional networks driving vertebrate dietary lipid responses.
BEYOND ZEBRAFISH:
Ingo Braasch (Michigan State University) described progress in establishing the spotted gar as a new non-teleost fish model for developmental and evolutionary genomics. The gar is a ‘living fossil’ with the slowest evolutionary rates among vertebrates and an “unduplicated” genome. Teleost fishes (zebrafish, medaka, killifish and cavefish) are important model systems for vertebrate biology and human disease; but because of a genome duplication in their common ancestor and their fast rates of sequence evolution, it is challenging to identify equivalent genomic regions in teleosts and humans. Armed with new genome assemblies, Braasch and his group have developed functional genomic tools like CRISPR genome editing for gar to show that many aspects of vertebrate biology were already present in the common ancestor of fish and human and did not occur as either teleost or tetrapod innovations.
LOOKING TO THE FUTURE: This was the focus of several regional community sessions held during the meeting. Funding uncertainties in the US, where priorities are undergoing a seismic shift, drove much of the conversations.
Two community sessions were held at the meeting: a regional session focused on local issues and a general session that introduced the IZFS and its mission to the entire group. The Americas regional community meeting began with a discussion of current developments in shipping fish between the U.S. and Canada, where fears of zebrafish carrying Spring Viremia of Carp has hobbled efforts at zebrafish import for many years. These fears have now spread to other countries (see the article on Shipping Zebrafish Internationally in this issue of the News Splash), so the experiences of Canadian researchers will be an important education in the future. To address this issue, the Special interest Group (SIG) of IZFS, the Canadian Zebrafish Research Community (CZRC) has created a line list, which references available zebrafish strains in Canada, and is ever growing and evolving. This list is only available to members of both IZFS and the CZRC SIG, to join the SIG for free, click here. We cover this important topic further in a full article in this issue of the News Splash (Shipping Zebrafish Internationally: Some Updates).
The Americas regional community meeting then turned to current challenges and uncertainties around NIH-funded research in the United States. The IZFC coincided with a meeting between NIH and FDA officials that indicated a turn away from research on animal models, particularly in the area of toxicology. The attendees at the session were exhorted to comment on the new priorities and to reach out to their elected representatives to articulate the importance of animal research and zebrafish research in particular. Since then, the NIH has released a clarification that, while re-iterating its intention to prioritize alternatives to animal research, recognized the importance of animal research to enhancing scientific knowledge.
The general community session focused on the IZFS and its mission. It recognized outgoing IZFS board members and welcomed the newly elected ones. It also recognized the efforts of many volunteers who serve on IZFS committees. The schedule of future meetings was shared; these will take place in Vienna in 2026 and Korea in 2027. PIs in the audience were reminded of the upcoming Strategic Conference of Zebrafish Investigators (SCZI), to be held in Singapore in January 2026 (registration and abstract submissions close tomorrow September 17th). Discussions on the location of Americas SCZI 2027 are still underway, with Mexico as the current front-runner.
A general sigh of disappointment went up around the room at the news that Kevin Thiessen, the name behind the ZebrafishRock! social media account, has decided to step away from managing the account. He provided an enormous and much-appreciated service to our community, particularly during the pandemic. Thank you, Kevin! Discussion ensued about how news would be shared amongst our membership after ZebrafishRock! retires. This newsletter is one important way. Furthermore, attendees were encouraged to join the ZebrafishRock! Slack channel, which is supported by ZFIN and is currently managed by Kevin though its management may transition to ZFIN staff in the future.
Finally, attendees at the community session discussed forging closer relations between the various zebrafish communities: the IZFS, the EZS, and the ZDMS. This effort has already begun, with the formation of joint inter-society committees: the Young Researcher Committee and the Environmental Sustainability Network. Future efforts of this kind will be essential to improving communication, reducing administrative burdens and perhaps reducing the number of zebrafish meetings that compete for our time and attention.
Overall, the 19th International Zebrafish Conference in Madison once again highlighted the exciting ongoing evolution of zebrafish scientific research, with a continuing broadening and deepening of the scope of this research. But it also reaffirmed the extent to which zebrafish researchers remain a cohesive community of colleagues invested in each others’ research success, and the success of the zebrafish research field as a whole. Katie Drerup (UW-Madison) shared that “the best part of the meeting is always reconnecting with colleagues. Especially during these stressful times, the genuine kindness, interest, and support of my fish friends made me excited again about our work.” With the potential for further difficult times ahead, it is important for us all to remember that our shared sense of purpose and community spirit have always been one of the greatest strengths of the zebrafish research field, strengths that we should all work even harder to continue to nurture in the future.