ZFIN ID: ZDB-LAB-990413-12
Yost Lab
PI/Director: Yost, H. Joseph
Contact Person: Upton, Teresa
Email: tupton@genetics.utah.edu
URL: http://yost.genetics.utah.edu/
Address: University of Utah Molecular Medicine Program Eccles Institute of Human Genetics Bldg. 533, Room 3160, 15 North 2030 East Salt Lake City, UT 84112-5330
Country: United States
Phone: 1-801-585-6110
Fax: 1-801-585-5470
Line Designation: zy

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What we do:

All animals start life as a single cell, the fertilized egg, which divides into hundreds of different cell types. Our long-term research goal is to understand the genes, molecules and developmental mechanisms that regulate the assignment of different cell identities in functionally appropriate positions in the developing vertebrate embryo, and to utilize this knowledge for the advancement of human medicine. This top-down approach utilizes embryonic phenotypes to uncover novel genetic pathways and cellular mechanisms ranging from extracellular signaling to genome-wide regulation of transcriptional networks.

Left-Right Axis Formation and Cilia

Our lab is a founder and leader in the field of vertebrate left-right development. Our research utilizes zebrafish, Xenopus and mice to discover the genes, molecular and cellular mechanisms that control asymmetric development of the brain, heart and gut. We have discovered novel mechanisms by which major cell-cell signaling pathways (FGF, TGFbeta and Wnt) control cilia function, cell migration and downstream pathways.

Cardiac Development

We are using genome-wide approaches to elucidate the Gene Regulatory Networks that control heart development in zebrafish, with the goal of understanding human complex congenital cardiac defects that are the leading cause of death in children in the first year. As one of four NHLBI-funded Cardiovascular Development Centers in the country, we have built a team developmental biologists, cardiac physiologists, and experts in chromatin structure, genome-wide gene network profiling, bioengineering and bioinformatics. We have created approaches that exclusively mark either polysomes or whole nuclei in a lineage-specific manor, allowing us to perform genome-wide expression profiling and analysis of the epigenome (RNA-Seq, ChIP-Seq, DNA bisulfite sequencing, etc) from rare cell lineages in the context of a whole animal at any stage of development. In parallel with our zebrafish cardiovascular projects, we have a collaborative project developing human amniocytes, which have nascent stem cell characteristics, into cardiomyocyte lineages with the long-term goal of clinical repair of human congenital heart defects.

Genomics in zebrafish

Driven by our interest in Gene Regulatory Networks in development and disease, and zebrafish's reputation for a challenging genome, we have created several molecular and bioinformatics approaches to discovering the molecular lesions of new mutations and rapidly identifying extant mutations. This will allow us to more fully manipulate the zebrafish genome in order to generate models systems of human genetic disorder, including specific cancers and complex heart disease.

The Glycocode Hypothesis

Heparan Sulfate Proteoglycans (HSPGs) are cell surface proteins with long chains of repeating sugar units (glycosaminoglycans; GAGs). Our discovery that a family of HSPGs control cell signaling pathways, cell migration and fibrillogenesis led to our focus on large gene families that regulate proteoglycan biochemistry and function. Our results suggest the existence of a "Glycocode" in which specific sulfation patterns on cell surface GAGs control specific cell-cell signaling decisions, including the modulation of Wnt, BMP and FGF signaling pathways. The Glycocode could provide enormous molecular diversity that dwarfs the informational content of the genome. Discovering out how this Glycocode is regulated and how it is utilized in biology will be one of the major challenges in the "postgenomic era" and will provide important therapeutic targets for a wide range of human diseases.

Barnette, Phillip Post-Doc Bisgrove, Brent Post-Doc Sato, Mariko Post-Doc
Yoshigi, Masaaki Post-Doc Cadwallader, Adam Graduate Student Neugebauer, Judith Graduate Student
Raelson, Kristel Graduate Student Sacayon, Patricia Graduate Student Barnette, Janet Research Staff
Harris, Erin Research Staff Hu, Norman Research Staff Shen, Jiaxiang Research Staff
Bush, Monica Fish Facility Staff Golafshani, Mohammad Fish Facility Staff Kim, Hyun-Chan Fish Facility Staff
Knight, Elise Administrative Staff Upton, Teresa Administrative Staff

Yates, J.D., Russell, R.C., Barton, N.J., Yost, H.J., Hill, J.T. (2021) A simple and rapid method for enzymatic synthesis of CRISPR-Cas9 sgRNA libraries. Nucleic acids research. 49(22):e131
Parvez, S., Herdman, C., Beerens, M., Chakraborti, K., Harmer, Z.P., Yeh, J.J., MacRae, C.A., Yost, H.J., Peterson, R.T. (2021) MIC-Drop: A platform for large-scale in vivo CRISPR screens. Science (New York, N.Y.). 373(6559):1146-1151
Keller, B.B., Kowalski, W.J., Tinney, J.P., Tobita, K., Hu, N. (2020) Validating the Paradigm That Biomechanical Forces Regulate Embryonic Cardiovascular Morphogenesis and Are Fundamental in the Etiology of Congenital Heart Disease. Journal of cardiovascular development and disease. 7(2)
Edwards, J.J., Rouillard, A.D., Fernandez, N.F., Wang, Z., Lachmann, A., Shankaran, S.S., Bisgrove, B.W., Demarest, B., Turan, N., Srivastava, D., Bernstein, D., Deanfield, J., Giardini, A., Porter, G., Kim, R., Roberts, A.E., Newburger, J.W., Goldmuntz, E., Brueckner, M., Lifton, R.P., Seidman, C.E., Chung, W.K., Tristani-Firouzi, M., Yost, H.J., Ma'ayan, A., Gelb, B.D. (2020) Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects. JACC. Basic to translational science. 5:376-386
Capasso, T.L., Li, B., Volek, H.J., Khalid, W., Rochon, E.R., Anbalagan, A., Herdman, C., Yost, H.J., Villanueva, F.S., Kim, K., Roman, B.L. (2019) BMP10-mediated ALK1 signaling is continuously required for vascular development and maintenance. Angiogenesis. 23(2):203-220
Jurynec, M.J., Bai, X., Bisgrove, B.W., Jackson, H., Nechiporuk, A., Palu, R.A.S., Grunwald, H.A., Su, Y.C., Hoshijima, K., Yost, H.J., Zon, L.I., Grunwald, D.J. (2019) The Paf1 Complex and P-TEFb have reciprocal and antagonist roles in maintaining multipotent neural crest progenitors. Development (Cambridge, England). 146(24):
Serrano, M.L.A., Demarest, B.L., Tone-Pah-Hote, T., Tristani-Firouzi, M., Yost, H.J. (2019) Inhibition of Notch signaling rescues cardiovascular development in Kabuki Syndrome. PLoS Biology. 17:e3000087
Abdul-Wajid, S., Demarest, B.L., Yost, H.J. (2018) Loss of embryonic neural crest derived cardiomyocytes causes adult onset hypertrophic cardiomyopathy in zebrafish. Nature communications. 9:4603
Karanth, S., Adams, J.D., Serrano, M.L.A., Quittner-Strom, E.B., Simcox, J., Villanueva, C.J., Ozcan, L., Holland, W.L., Yost, H.J., Vella, A., Schlegel, A. (2018) A Hepatocyte FOXN3-α Cell Glucagon Axis Regulates Fasting Glucose. Cell Reports. 24:312-319
Jin, Y.N., Schlueter, P.J., Jurisch-Yaksi, N., Lam, P.Y., Jin, S., Hwang, W.Y., Yeh, J.J., Yoshigi, M., Ong, S.E., Schenone, M., Hartigan, C.R., Carr, S.A., Peterson, R.T. (2018) Noncanonical translation via deadenylated 3' UTRs maintains primordial germ cells. Nature Chemical Biology. 14(9):844-852
Bisgrove, B.W., Su, Y.C., Yost, H.J. (2017) Maternal Gdf3 is an obligatory cofactor in nodal signaling for embryonic axis formation in zebrafish. eLIFE. 6
Hill, J.T., Demarest, B., Smith, M., Gorsi, B., Yost, H.J. (2017) Heart morphogenesis gene regulatory networks revealed by temporal expression analysis. Development (Cambridge, England). 144(19):3487-3498
Shankaran, S.S., Dahlem, T.J., Bisgrove, B.W., Yost, H.J., Tristani-Firouzi, M. (2017) CRISPR/Cas9-Directed Gene Editing for the Generation of Loss-of-Function Mutants in High-Throughput Zebrafish F0 Screens.. Current protocols in molecular biology. 119:31.9.1-31.9.22
Karanth, S., Zinkhan, E.K., Hill, J.T., Yost, H.J., Schlegel, A. (2016) FOXN3 Regulates Hepatic Glucose Utilization. Cell Reports. 15(12):2745-55
Poulain, F.E., Yost, H.J. (2015) Heparan sulfate proteoglycans: a sugar code for vertebrate development?. Development (Cambridge, England). 142:3456-67
Percival, S.M., Thomas, H.R., Amsterdam, A., Carroll, A.J., Lees, J.A., Yost, H.J., Parant, J.M. (2015) Variations in sister chromatid cohesion dysfunction in esco2 mutant zebrafish reflects the phenotypic diversity of Roberts Syndrome. Disease models & mechanisms. 8(8):941-55
Nash, D., Arrington, C.B., Kennedy, B.J., Yandell, M., Wu, W., Zhang, W., Ware, S., Jorde, L.B., Gruber, P.J., Yost, H.J., Bowles, N.E., Bleyl, S.B. (2015) Shared Segment Analysis and Next-Generation Sequencing Implicates the Retinoic Acid Signaling Pathway in Total Anomalous Pulmonary Venous Return (TAPVR). PLoS One. 10:e0131514
Samson, S.C., Ferrer, T., Jou, C.J., Sachse, F.B., Shankaran, S.S., Shaw, R.M., Chi, N.C., Tristani-Firouzi, M., and Yost, H.J. (2013) 3-OST-7 regulates BMP-dependent cardiac contraction. PLoS Biology. 11(12):e1001727
Arrington, C.B., Peterson, A.G., and Yost, H.J. (2013) Sdc2 and Tbx16 regulate Fgf2-dependent epithelial cell morphogenesis in the ciliated organ of asymmetry. Development (Cambridge, England). 140(19):4102-4109
Peterson, A.G., Wang, X., and Yost, H. J. (2013) Dvr1 transfers left-right asymmetric signals from Kupffer's vesicle to lateral plate mesoderm in zebrafish. Developmental Biology. 382(1):198-208
Neugebauer, J.M., Cadwallader, A.B., Amack, J.D., Bisgrove, B.W., and Yost, H.J. (2013) Differential roles for 3-OSTs in the regulation of cilia length and motility. Development (Cambridge, England). 140(18):3892-3902
Lafontant, P.J., Behzad, A.R., Brown, E., Landry, P., Hu, N., and Burns, A.R. (2013) Cardiac myocyte diversity and a fibroblast network in the junctional region of the zebrafish heart revealed by transmission and serial block-face scanning electron microscopy. PLoS One. 8(8):e72388
Hill, J.T., Demarest, B.L., Bisgrove, B.W., Gorsi, B., Su, Y.C., and Yost, H.J. (2013) MMAPPR: Mutation Mapping Analysis Pipeline for Pooled RNA-seq. Genome research. 23(4):687-697
Tay, H.G., Schulze, S.K., Compagnon, J., Foley, F.C., Heisenberg, C.P., Yost, H.J., Abdelilah-Seyfried, S., and Amack, J.D. (2013) Lethal giant larvae 2 regulates development of the ciliated organ Kupffer's vesicle. Development (Cambridge, England). 140(7):1550-1559
Wang, G., Yost, H.J., and Amack, J.D. (2013) Analysis of Gene Function and Visualization of Cilia-Generated Fluid Flow in Kupffer's Vesicle. Journal of visualized experiments : JoVE. (73)
Jurisch-Yaksi, N., Rose, A.J., Lu, H., Raemaekers, T., Munck, S., Baatsen, P., Baert, V., Vermeire, W., Scales, S.J., Verleyen, D., Vandepoel, R., Tylzanowski, P., Yaksi, E., de Ravel, T., Yost, H.J., Froyen, G., Arrington, C.B., and Annaert, W. (2013) Rer1p maintains ciliary length and signaling by regulating γ-secretase activity and Foxj1a levels. The Journal of cell biology. 200(6):709-720
Eisenhoffer, G.T., Loftus, P.D., Yoshigi, M., Otsuna, H., Chien, C.B., Morcos, P.A., and Rosenblatt, J. (2012) Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia. Nature. 484(7395):546-549
Cadwalader, E.L., Condic, M.L., and Yost, H.J. (2012) 2-O-sulfotransferase regulates Wnt signaling, cell adhesion and cell cycle during zebrafish epiboly. Development (Cambridge, England). 139(7):1296-1305
Bisgrove, B.W., Makova, S., Yost, H.J., and Brueckner, M. (2012) RFX2 is essential in the ciliated organ of asymmetry and an RFX2 transgene identifies a population of ciliated cells sufficient for fluid flow. Developmental Biology. 363(1):166-178
Wythe, J.D., Jurynec, M.J., Urness, L.D., Jones, C.A., Sabeh, M.K., Werdich, A.A., Sato, M., Yost, H.J., Grunwald, D.J., MacRae, C.A., and Li, D.Y. (2011) Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish. Disease models & mechanisms. 4(5):607-21
Wang, G., Cadwallader, A.B., Jang, D.S., Tsang, M., Yost, H.J., and Amack, J.D. (2011) The Rho kinase Rock2b establishes anteroposterior asymmetry of the ciliated Kupffer's vesicle in zebrafish. Development (Cambridge, England). 138(1):45-54
Parant, J.M., George, S.A., Holden, J.A., and Yost, H.J. (2010) Genetic modeling of Li-Fraumeni syndrome in zebrafish. Disease models & mechanisms. 3(1-2):45-56
Parant, J.M., George, S.A., Pryor, R., Wittwer, C.T., and Yost, H.J. (2009) A rapid and efficient method of genotyping zebrafish mutants. Developmental dynamics : an official publication of the American Association of Anatomists. 238(12):3168-3174
Arrington, C.B., and Yost, H.J. (2009) Extra-embryonic syndecan 2 regulates organ primordia migration and fibrillogenesis throughout the zebrafish embryo. Development (Cambridge, England). 136(18):3143-3152
Neugebauer, J.M., Amack, J.D., Peterson, A.G., Bisgrove, B.W., and Yost, H.J. (2009) FGF signalling during embryo development regulates cilia length in diverse epithelia. Nature. 458(7238):651-654
Wang, X., and Yost, H.J. (2008) Initiation and propagation of posterior to anterior (PA) waves in zebrafish left-right development. Developmental dynamics : an official publication of the American Association of Anatomists. 237(12):3640-3647
Wolman, M.A., Sittaramane, V., Essner, J.J., Yost, H.J., Chandrasekhar, A., and Halloran, M.C. (2008) Transient axonal glycoprotein-1 (TAG-1) and laminin-alpha1 regulate dynamic growth cone behaviors and initial axon direction in vivo. Neural Development. 3:6
Kwan, K.M., Fujimoto, E., Grabher, C., Mangum, B.D., Hardy, M.E., Campbell, D.S., Parant, J.M., Yost, H.J., Kanki, J.P., and Chien, C.B. (2007) The Tol2kit: A multisite gateway-based construction kit for Tol2 transposon transgenesis constructs. Developmental dynamics : an official publication of the American Association of Anatomists. 236(11):3088-3099
Amack, J.D., Wang, X., and Yost, H.J. (2007) Two T-box genes play independent and cooperative roles to regulate morphogenesis of ciliated Kupffer's vesicle in zebrafish. Developmental Biology. 310(2):196-210
Tsai, I.C., Amack, J.D., Gao, Z.H., Band, V., Yost, H.J., and Virshup, D.M. (2007) A Wnt-CKIε-Rap1 Pathway Regulates Gastrulation by Modulating SIPA1L1, a Rap GTPase Activating Protein. Developmental Cell. 12(3):335-347
Cadwallader, A.B., and Yost, H.J. (2007) Combinatorial expression patterns of heparan sulfate sulfotransferases in zebrafish: III. 2-O-sulfotransferase and C5-epimerases. Developmental dynamics : an official publication of the American Association of Anatomists. 236(2):581-6
Takeuchi, J.K., Lickert, H., Bisgrove, B.W., Sun, X., Yamamoto, M., Chawengsaksophak, K., Hamada, H., Yost, H.J., Rossant, J., and Bruneau, B.G. (2007) Baf60c is a nuclear Notch signaling component required for the establishment of left-right asymmetry. Proceedings of the National Academy of Sciences of the United States of America. 104(3):846-851
Cadwallader, A.B., and Yost, H.J. (2006) Combinatorial expression patterns of heparan sulfate sulfotransferases in zebrafish: I. The 3-O-sulfotransferase family. Developmental dynamics : an official publication of the American Association of Anatomists. 235(12):3423-3431
Cadwallader, A.B., and Yost, H.J. (2006) Combinatorial expression patterns of heparan sulfate sulfotransferases in zebrafish: II. The 6-O-sulfotransferase family. Developmental dynamics : an official publication of the American Association of Anatomists. 235(12):3432-3437
Sato, M., Tsai, H.J., and Yost, H.J. (2006) Semaphorin3D regulates invasion of cardiac neural crest cells into the primary heart field. Developmental Biology. 298(1):12-21
Nadauld, L.D., Chidester, S., Shelton, D.N., Rai, K., Broadbent, T., Sandoval, I.T., Peterson, P.W., Manos, E.J., Ireland, C.M., Yost, H.J., and Jones, D.A. (2006) Dual roles for adenomatous polyposis coli in regulating retinoic acid biosynthesis and Wnt during ocular development. Proceedings of the National Academy of Sciences of the United States of America. 103(36):13409-13414
Bisgrove, B.W., Snarr, B.S., Emrazian, A., and Yost, H.J. (2005) Polaris and Polycystin-2 in dorsal forerunner cells and Kupffer's vesicle are required for specification of the zebrafish left-right axis. Developmental Biology. 287(2):274-288
Nadauld, L.D., Shelton, D.N., Chidester, S., Yost, H.J., and Jones, D.A. (2005) The zebrafish retinol dehydrogenase, rdh1l, is essential for intestinal development and is regulated by the tumor suppressor adenomatous polyposis coli. The Journal of biological chemistry. 280(34):30490-30495
Essner, J.J., Amack, J.D., Nyholm, M.K., Harris, E.B., and Yost, H.J. (2005) Kupffer's vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left-right development of the brain, heart and gut. Development (Cambridge, England). 132(6):1247-1260
Nadauld, L.D., Sandoval, I.T., Chidester, S., Yost, H.J., and Jones, D.A. (2004) Adenomatous polyposis coli control of retinoic acid biosynthesis is critical for zebrafish intestinal development and differentiation. The Journal of biological chemistry. 279(49):51581-51589
Amack, J.D., and Yost, H.J. (2004) The T box transcription factor no tail in ciliated cells controls zebrafish left-right asymmetry. Current biology : CB. 14(8):685-690
Liang, P., Jones, C.A., Bisgrove, B.W., Song, L., Glenn, S.T., Yost, H.J., and Gross, K.W. (2004) Genomic characterization and expression analysis of the first non-mammalian renin genes from zebrafish and pufferfish. Physiological Genomics. 16(3):314-322
Goering, L.M., Hoshijima, K., Hug, B., Bisgrove, B., Kispert, A., and Grunwald, D.J. (2003) An interacting network of T-box genes directs gene expression and fate in the zebrafish mesoderm. Proceedings of the National Academy of Sciences of the United States of America. 100(16):9410-9415
Sato, M. and Yost, H.J. (2003) Cardiac neural crest contributes to cardiomyogenesis in zebrafish. Developmental Biology. 257(1):127-139
Bisgrove, B.W., Morelli, S.H., and Yost, H.J. (2003) Genetics of human laterality disorders: insights from vertebrate model systems. Annual review of genomics and human genetics. 4:1-32
Kramer, K.L. and Yost, H.J. (2003) Heparan sulfate core proteins in cell-cell signaling. Annual review of genetics. 37:461-484
Sato, M. and Yost, H.J. (2002) Do cardiac neural crest defects in zebrafish result in loss of cardiomyocytes?. Developmental Biology. 247(2):508
Prescott, S.M. and Yost, H.J. (2002) The COXes of Danio: from mechanistic model to experimental therapeutics. Proceedings of the National Academy of Sciences of the United States of America. 99(14):9084-9086
Essner, J.J., Vogan, K.J., Wagner, M.K., Tabin, C.J., Yost, H.J., and Brueckner, M. (2002) Conserved function for embryonic nodal cilia. Nature. 418(6893):37-38
Morgan, D., Goodship, J., Essner, J.J., Vogan, K.J., Turnpenny, L., Yost, J., Tabin, C.J., and Strachan, T. (2002) The left-right determinant inversin has highly conserved ankyrin repeat and IQ domains and interacts with calmodulin. Human genetics. 110(4):377-384
Kramer, K.L. and Yost, H.J. (2002) Cardiac left-right development: are the early steps conserved?. Cold Spring Harbor symposia on quantitative biology. 67:37-43
Hu, N., Yost, H.J., and Clark, E.B. (2001) Cardiac morphology and blood pressure in the adult zebrafish. The Anatomical record. 264(1):1-12
Bisgrove, B.W. and Yost, H.J. (2001) Classification of left-right patterning defects in zebrafish, mice, and humans. American journal of medical genetics. 101(4):315-323
Essner, J.J., Wang, X.H., Zhang, J., and Yost, H.J. (2001) The zebrafish inv gene is required for left-right brain and heart development. Developmental Biology. 235(1):181 (#44)
Hu, N., Clark, E.B., and Yost, H.J. (2001) Cardiac morphology and blood pressure in the adult zebrafish. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 15(5):A1231
Hu, N., Sedmera, D., Yost, H.J., and Clark, E.B. (2000) Structure and function of the developing zebrafish heart. The Anatomical record. 260(2):148-157
Bisgrove, B.W., Essner, J.J., Yost, H.J. (2000) Multiple pathways in the midline regulate concordant brain, heart and gut left-right asymmetry. Development (Cambridge, England). 127(16):3567-3579
Angelo, S., Lohr, J., Lee, K.H., Ticho, B.S., Breitbart, R.E., Hill, S., Yost, H.J., and Srivastava, D. (2000) Conservation of sequence and expression of Xenopus and zebrafish dHAND during cardiac, branchial arch and lateral mesoderm development. Mechanisms of Development. 95(1-2):231-237
Essner, J.J., Branford, W.W., Zhang, J., and Yost, H.J. (2000) Mesendoderm and left-right brain, heart and gut development are differentially regulated by pitx2 isoforms. Development (Cambridge, England). 127(5):1081-1093
Lohr, J.L. and Yost, J. (2000) Vertebrate model systems in the study of early heart development: Xenopus and zebrafish. American journal of medical genetics. 97(4):248-257
Bisgrove, B.W., Essner, J.J., and Yost, H.J. (1999) Regulation of midline development by antagonism of lefty and nodal signaling. Development (Cambridge, England). 126(14):3253-3262
Ramsdell, A.F. and Yost, H.J. (1998) Molecular mechanisms of vertebrate left–right development. Trends in genetics : TIG. 14(11):459-465
Yost, H.J. (1998) The genetics of midline and cardiac laterality defects. Current opinion in cardiology. 13:185-189
Yost, H.J. (1998) Left-right development in Xenopus and zebrafish. Seminars in cell & developmental biology. 9:61-66
Bisgrove, B.W., Raible, D.W., Walter, V., Eisen, J.S., and Grunwald, D.J. (1997) Expression of c-ret in the zebrafish embryo: potential roles in motoneuronal development. Journal of neurobiology. 33(6):749-768
Liao, W., Bisgrove, B.W., Sawyer, H., Hug, B., Bell, B., Peters, K., Grunwald, D.J., and Stainier, D.Y.R. (1997) The zebrafish gene cloche acts upstream of a flk-1 homologue to regulate endothelial cell differentiation. Development (Cambridge, England). 124(2):381-389
Danos, M.C. and Yost, H.J. (1996) Role of notochord in specification of cardiac left-right orientation in zebrafish and Xenopus. Developmental Biology. 177:96-103