Yale Zebrafish Research Core
Basement, 300 George St.
About the core
Mission
The Yale Zebrafish Research Core (YZRC) was founded with two goals: one, to model human diseases in zebrafish with the long-term goal of facilitating small molecule screens for novel therapies; and two, to lower the barrier of entry for Yale investigators seeking to carry out experiments in zebrafish.
Why zebrafish?
Zebrafish possess many advantages over other model systems. They are optically transparent throughout much of early development, greatly facilitating live imaging studies. The zebrafish genome is of excellent quality and fish-specific transgenic tools are very mature and efficient. Thousands of zebrafish can be generated by a single crossing, and the resultant larvae are fully active, behaving vertebrate organisms within days of fertilization. Zebrafish larvae are also small enough to fit happily into a 96-well plate format. Taken together, these factors make zebrafish a uniquely powerful model for performing chemical or genetic screens.
Examples of disease modeling in zebrafish
A multitude of diseases have been successfully modeled in zebrafish, both in the YZRC and elsewhere. Many of these involve generating specific mutants or transgenics, but other approaches are possible. Please consider the following examples as inspiration!
Jump to: Cardiovascular disease * Cancer * Meningitis * Rare and congenital diseases * Autism
Cardiovascular disease
A human patient population prone to intracranial hemorrhages was identified and exome-sequenced by Yale researchers. A candidate mutation was introduced into zebrafish; this was sufficient to generate hemorrhages and necrosis in larval zebrafish (arrowheads). (Barak et al. 2021)
Cancer
Pigment cells are derived from a transient embryonic cell type known as the neural crest. Mutations in receptor tyrosine kinase signaling have been shown to influence cell fate acquisition, resulting in pigment and organ development phenotypes (see figure to the right showing the pigment phenotype). Recently, Yale researchers identified novel ligands of the Ltk receptor tyrosine kinase known as Augmentors. Mutations in these Augmentor genes also generate pigment phenotypes. Understanding signaling in pigment cells has critical relevance to disease—a melanoma model generated in fish that closely resembles human melanoma has been shown to recapitulate aspects of neural crest development. (CITATIONS)
Meningitis
In humans, bacterial meningitis causes headaches, fever, seizures, and neck stiffness. Many of these symptoms are replicated in a zebrafish model of the disease in which Streptococcus pneumoniae is injected into the hindbrain ventricle. Neurons in contact with the cerebrospinal fluid respond to bitter-tasting metabolites secreted by bacteria, and this response can be monitored in vivo in real-time using genetically-encoded calcium indicators. (Prendergast et al. 2023)
Rare and congenital diseases
Several zebrafish mutants have been identified which exhibit progressively worsening scoliosis. Rescuing the function of particular genes (in this case ptk7) is sufficient to rescue scoliotic phenotypes. Human patients with idiopathic scoliosis have also been found to carry missense mutations in the ptk7 gene. (Hayes et al. 2014)
Autism spectrum disorder
Available to Yale researchers & external researchers
Core website
Onboarding & ordering
The zebrafish core is a full-service research core that is happy to plan, execute, and analyze experiments end-to-end with minimal user input. As a customer, you are free to determine your level of involvement. We are always happy to accept and train your own staff at any level of expertise should you wish to be more hands-on. If you wish to have full access to the facility and its equipment, you will need to follow the steps outlined here: Steps for facility access.
Resources
Plasmid database: This is a list of vectors we currently have stored in the lab. We are happy to distribute these on request.
Antibody database: This is a list of antibodies we currently have on hand. If you require antibodies not listed here for immunofluorescence, we will need to order these and will charge them to you as a pass-through.
Shareable fish lines: These are fish in our facility that are not part of a faculty-specific project which we are happy to share with you. Alternately, any of these lines can serve as the base material for any mutants or transgenics you wish to generate.
Publications
Modeling thoracic aortic genetic variants in the zebrafish: useful for predicting clinical pathogenicity?Prendergast A, Sheppard MB, Famulski JK, Nicoli S, Mukherjee S, Sips P, Elefteriades JA. Front Cardiovasc Med. 2025; 2025 Feb 19. PMID: 40066353.
Akt is a mediator of artery specification during zebrafish development. Zhou W, Ghersi JJ, Ristori E, Semanchik N, Prendergast A, Zhang R, Carneiro P, Baldissera G, Sessa WC, Nicoli S. Development. 2024 Sep 1; 2024 Sep 2. PMID: 39101673.
Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions Tanaka K, Chen M, Prendergast A, Zhuang Z, Nasiri A, Joshi D, Hintzen J, Chung M, Kumar A, Mani A, Koleske A, Crawford J, Nicoli S, Schwartz MA. EMBO J. 2024 Aug; 2024 Jun 17. PMID: 38886581.
Piloting the adaptation of the Kaufman Assessment Battery for Children-2 (nd) edition (KABC-II) to assess school-age neurodevelopment in rural Zimbabwe. Piper JD, Mazhanga C, Mapako G, Mapurisa I, Mashedze T, Munyama E, Mwapaura M, Chidhanguro D, Gerema G, Tavengwa NV, Ntozini R, Langhaug LF, Smuk M, Rochat T, Kaufman A, Kaufman N, Gladstone M, Allen E, Prendergast AJ. Wellcome Open Res. 2022; 2024 May 30. PMID: 38910935.
High NaCl Concentrations in Water Are Associated with Developmental Abnormalities and Altered Gene Expression in Zebrafish. Seli DA, Prendergast A, Ergun Y, Tyagi A, Taylor HS. Int J Mol Sci. 2024 Apr 7; 2024 Apr 7. PMID: 38612913.
Reply to Pisan et al.: Pathogenicity of inherited TRAF7 mutations in congenital heart disease. Mishra-Gorur K, Barak T, Kaulen LD, Henegariu O, Jin SC, Aguilera SM, Yalbir E, Goles G, Nishimura S, Miyagishima D, Djenoune L, Altinok S, Rai DK, Viviano S, Prendergast A, Zerillo C, Ozcan K, Baran B, Sencar L, Goc N, Yarman Y, Ercan-Encicek AG, Bilguvar K, Lifton RP, Moliterno J, Louvi A, Yuan S, Deniz E, Brueckner M, Gunel M. Proc Natl Acad Sci U S A. 2024 Mar 19; 2024 Mar 11. PMID: 38466853.
Differences in Mental Illness Stigma by Disorder and Gender: Population-Based Vignette Randomized Experiment in Rural Uganda. Lee YJ, Christ R, Mbabazi R, Dabagia J, Prendergast A, Wykoff J, Dasari S, Safai D, Nakaweesi S, Aturinde SR, Galvin M, Akena D, Ashaba S, Waiswa P, Rosenheck R, Tsai AC. PLOS Ment Health. 2024; 2024 Jun 21. PMID: 39188639.
Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations. Zhao S, Mekbib KY, van der Ent MA, Allington G, Prendergast A, Chau JE, Smith H, Shohfi J, Ocken J, Duran D, Furey CG, Hao LT, Duy PQ, Reeves BC, Zhang J, Nelson-Williams C, Chen D, Li B, Nottoli T, Bai S, Rolle M, Zeng X, Dong W, Fu PY, Wang YC, Mane S, Piwowarczyk P, Fehnel KP, See AP, Iskandar BJ, Aagaard-Kienitz B, Moyer QJ, Dennis E, Kiziltug E, Kundishora AJ, DeSpenza T Jr, Greenberg ABW, Kidanemariam SM, Hale AT, Johnston JM, Jackson EM, Storm PB, Lang SS, Butler WE, Carter BS, Chapman P, Stapleton CJ, Patel AB, Rodesch G, Smajda S, Berenstein A, Barak T, Erson-Omay EZ, Zhao H, Moreno-De-Luca A, Proctor MR, Smith ER, Orbach DB, Alper SL, Nicoli S, Boggon TJ, Lifton RP, Gunel M, King PD, Jin SC, Kahle KT. Nat Commun. 2023 Nov 17; 2023 Nov 17. PMID: 37978175.
Pleiotropic role of TRAF7 in skull-base meningiomas and congenital heart disease. Mishra-Gorur K, Barak T, Kaulen LD, Henegariu O, Jin SC, Aguilera SM, Yalbir E, Goles G, Nishimura S, Miyagishima D, Djenoune L, Altinok S, Rai DK, Viviano S, Prendergast A, Zerillo C, Ozcan K, Baran B, Sencar L, Goc N, Yarman Y, Ercan-Sencicek AG, Bilguvar K, Lifton RP, Moliterno J, Louvi A, Yuan S, Deniz E, Brueckner M, Gunel M. Proc Natl Acad Sci U S A. 2023 Apr 18; 2023 Apr 12. PMID: 37043537.
Phenotyping Zebrafish Mutant Models to Assess Candidate Genes Associated with Aortic Aneurysm. Prendergast A, Ziganshin BA, Papanikolaou D, Zafar MA, Nicoli S, Mukherjee S, Elefteriades JA. Genes (Basel). 2022 Jan 10; 2022 Jan 10. PMID: 35052463.
PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans.Barak T, Ristori E, Ercan-Sencicek AG, Miyagishima DF, Nelson-Williams C, Dong W, Jin SC, Prendergast A, Armero W, Henegariu O, Erson-Omay EZ, Harmancı AS, Guy M, Gültekin B, Kilic D, Rai DK, Goc N, Aguilera SM, Gülez B, Altinok S, Ozcan K, Yarman Y, Coskun S, Sempou E, Deniz E, Hintzen J, Cox A, Fomchenko E, Jung SW, Ozturk AK, Louvi A, Bilgüvar K, Connolly ES Jr, Khokha MK, Kahle KT, Yasuno K, Lifton RP, Mishra-Gorur K, Nicoli S, Günel M. Nat Med. 2021 Dec; 2021 Dec 9. PMID: 34887573.
Glia: A Gate Controlling Animal Behavior? Wyart C, Prendergast A. Curr Biol. 2019 Sep 9. PMID: 31505186.
Acknowledgment
If research supported by this research core results in publication, please acknowledge this support by including the following in your publication(s): "We thank the Yale Zebrafish Phenotyping Core for Precision Medicine for their assistance with..."
Rates
| Service | Internal client | External nonprofit client | External for-profit client |
|---|---|---|---|
| Making a fish line (CRISPR-Cas9/Tol2/phiC31) | $8,500 | $13,000 | Contact us |
| Making a fish line (homology-directed repair) | $12,500 | $19,500 | |
| Phenotyping group 1 (plasmid/mRNA/CRISPR-Cas9 injection F0) | $1,250 | $2,000 | |
| Phenotyping group 2 (immunohistochemistry) | $645 | $1,150 | |
| Phenotyping: Imaging | $525 | $900 | |
| Behavioral phenotyping | $200 | ||
| Phenotyping: Monitoring | $200 | $400 | |
| Genotyping | $35 | $225 | |
| In vitro fertilization | $300 | ||
| Basic training | $400 | ||
| Consultation | $250 | $475 | |
| Protocol, grant, & manuscript assistance | $650 | ||
| Using Zebrafish Core equipment unassisted | $75 | ||
| Cryopreservation | $500 | $800 | |
| Molecular cloning: One-step LR gateway reaction | $500 | $750 | |
| Molecular cloning: Two-step cloning (pENTR5’ or pME + LR gateway reaction) | $1,000 | $1700 | |
| Staff service | $59.52/hr |
Contacts
Facilities are in the basement of 300 George St., New Haven. Please see Onboarding & ordering section for information on getting access.
Faculty Director
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Core/facility
Aberration-Corrected Electron Microscopy (ACEM) Core
Our core's focus is cutting-edge and high-throughput capability in electron microscopy techniques, including TEM, SEM, and FIB.
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Core/facility
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Core/facility
Keck Biophysical Resource
We offer resources to study the oligomeric state of biomolecular assemblies as well as the thermodynamics and kinetics of macromolecular interactions.
Ewa Folta-Stogniew, PhD, MSc
Director (Retired)