ZFIN ID: ZDB-LAB-051026-1
Scott Laboratory
PI/Director: Scott, Ian
Contact Person: Scott, Ian
Email: ian.scott@sickkids.ca
URL: https://lab.research.sickkids.ca/scott/
Address: The Hospital for Sick Children The Peter Gilgan Centre for Research and Learning 686 Bay Street Rm 16.9707 Toronto, ON M5G 0A4 Canada
Country: Canada
Phone: 416- 813-7654 x301572
Fax:
Line Designation: hsc


GENOMIC FEATURES ORIGINATING FROM THIS LAB
Show first 50 of 79 genomic features


STATEMENT OF RESEARCH INTERESTS
RESEARCH INTERESTS:

- specification and development of cardiovascular progenitor cells
- the zebrafish second heart field
- cranial vasculature development/CCMs
- early heart development
- Apelin receptor signaling

RESEARCH ACTIVITIES:

The lab is focused on on how cardiac fate is first established, and how the heart later grows and develops. Using the advantages of the zebrafish embryo, we employ genetic, embryological, live imaging and biochemical approaches to study in real time the earliest events of cardiovascular development. Current research topics include: 1) role of Aplnr signalling in migration of cardiac progenitors to the heart-forming region; 2) transcriptional control of early cardiac fate and migration; 3) regulation of second heart field (SHF) development; and 4) role of CCM3 signalling in cranial vasculature development.

Previous work on the zebrafish grinch mutant has highlighted the role of the Aplnr GPCR in early heart development. We have found that Aplnr signalling regulates migration of cardiac progenitors during gastrulation in a non cell-autonomous manner. Currently, we are examining how Aplnr signalling effectuates this key function. In a complementary set of approaches, we have found that a combination of the transcription factors Gata5 and Smarcd3/Baf60c is sufficient to direct cells placed in regions of the embryo normally fated to form non-cardiac structures to migrate to the heart-forming region and adopt a cardiovascular fate. Gata5/Smarcd3 therefore appear to have a remarkable "pro-cardiac progenitor" activity. We are currently evaluating the molecular pathways that act downstream of Gata5/Smarcd3.

Other research in the lab focuses on later aspects of cardiovascular development. We were among the first to show that development of the zebrafish heart is driven in part by addition of cells analogous to the mammalian second heart field (SHF). As defects in SHF development are causative of a large variety of congenital heart defects, we are using the zebrafish embryo to uncover novel regulators of SHF development. We have further uncovered a novel molecular pathway for pathogenesis of cranial cavernous malformations (CCMs), dilatations of the cranial vasculature that can lead to hemorrhages, seizures and death. We have found that CCM3 acts in an apparently CCM1/2-independent fashion in a zebrafish model of CCMs. Currently, we are examining the mechanism by which CCM3 regulates cranial vasculature development.

It is hoped that by combining genetic, embryological and imaging approaches we will gain a deeper understanding of the developmental processes that regulate heart development. In the future, we hope to apply this knowledge to therapeutic approaches for congenital and adult-onset cardiovascular disease.

FUTURE RESEARCH INTERESTS:

- application of cardiovascular progenitor cell pathways to vertebrate heart regeneration
- use of chemical genetic approaches to both study heart development and explore using small molecules to alleviate zebrafish genetic models of congenital heart defects
- examination of diversity and cell fate choices in cardiac progenitor populations


LAB MEMBERS
Leslie, Meaghan Graduate Student Onderisin, Chris Graduate Student Rosenthal, Shimon Graduate Student
Yuan, Xuefei Graduate Student McDonald, Laura Research Staff


ZEBRAFISH PUBLICATIONS OF LAB MEMBERS
Lee, S.H., Hadipour-Lakmehsari, S., Murthy, H.R., Gibb, N., Miyake, T., Teng, A.C.T., Cosme, J., Yu, J.C., Moon, M., Lim, S., Wong, V., Liu, P., Billia, F., Fernandez-Gonzalez, R., Stagljar, I., Sharma, P., Kislinger, T., Scott, I.C., Gramolini, A.O. (2020) REEP5 depletion causes sarco-endoplasmic reticulum vacuolization and cardiac functional defects. Nature communications. 11:965
Yuan, X., Song, M., Devine, P., Bruneau, B.G., Scott, I.C., Wilson, M.D. (2018) Heart enhancers with deeply conserved regulatory activity are established early in zebrafish development. Nature communications. 9:4977
Gibb, N., Lazic, S., Yuan, X., Deshwar, A.R., Leslie, M., Wilson, M.D., Scott, I.C. (2018) Hey2 regulates the size of the cardiac progenitor pool during vertebrate heart development. Development (Cambridge, England). 145(22):
Zhang, L., Yang, Y., Li, B., Scott, I.C., Lou, X. (2018) The DEAD box RNA helicase Ddx39ab is essential for myocyte and lens development in zebrafish. Development (Cambridge, England). 145(8)
Ma, D., Tu, C., Sheng, Q., Yang, Y., Kan, Z., Guo, Y., Shyr, Y., Scott, I.C., Lou, X. (2018) Dynamics of zebrafish heart regeneration using an HPLC-ESI-MS/MS approach. Journal of Proteome Research. 17(3):1300-1308
Razaghi, B., Steele, S.L., Prykhozhij, S.V., Stoyek, M.R., Hill, J.A., Cooper, M.D., McDonald, L., Lin, W., Daugaard, M., Crapoulet, N., Chacko, S., Lewis, S., Scott, I.C., Sorensen, P.H.B., Berman, J.N. (2017) hace1 influences zebrafish cardiac development via ROS-dependent mechanisms. Developmental dynamics : an official publication of the American Association of Anatomists. 247(2):289-303
Kenney, J.W., Scott, I.C., Josselyn, S.A., Frankland, P.W. (2017) Contextual fear conditioning in zebrafish. Learning & memory (Cold Spring Harbor, N.Y.). 24:516-523
Hou, N., Yang, Y., Scott, I.C., Lou, X. (2017) The Sec domain protein Scfd1 facilitates trafficking of ECM components during chondrogenesis. Developmental Biology. 421(1):8-15
Deshwar, A.R., Onderisin, J.C., Aleksandrova, A., Yuan, X., Burrows, J.T., Scott, I.C. (2016) Mespaa can potently induce cardiac fates in zebrafish. Developmental Biology. 418(1):17-27
Hanwell, D., Hutchinson, S.A., Collymore, C., Bruce, A.E., Louis, R., Ghalami, A., Allison, W.T., Ekker, M., Eames, B.F., Childs, S., Kurrasch, D.M., Gerlai, R., Thiele, T., Scott, I., Ciruna, B., Dowling, J.J., McFarlane, S., Huang, P., Wen, X.Y., Akimenko, M.A., Waskiewicz, A.J., Drapeau, P., Babiuk, L.A., Dragon, D., Smida, A., Buret, A.G., O'Grady, E., Wilson, J., Sowden-Plunkett, L., Tropepe, V. (2016) Restrictions on the Importation of Zebrafish into Canada Associated with Spring Viremia of Carp Virus. Zebrafish. 13 Suppl 1:S153-63
Deshwar, A.R., Chng, S.C., Ho, L., Reversade, B., Scott, I.C. (2016) The Apelin receptor enhances Nodal/TGFβ signaling to ensure proper cardiac development. eLIFE. 5
Lou, X., Burrows, J.T., Scott, I.C. (2015) Med14 cooperates with brg1 in the differentiation of skeletogenic neural crest. BMC Developmental Biology. 15:41
Sharma, P., Abbasi, C., Lazic, S., Teng, A.C., Wang, D., Dubois, N., Ignatchenko, V., Wong, V., Liu, J., Araki, T., Tiburcy, M., Ackerley, C., Zimmermann, W.H., Hamilton, R., Sun, Y., Liu, P.P., Keller, G., Stagljar, I., Scott, I.C., Kislinger, T., Gramolini, A.O. (2015) Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function. Nature communications. 6:8391
Burrows, J.T., Pearson, B.J., Scott, I.C. (2015) An In Vivo Requirement for the Mediator Subunit Med14 in the Maintenance of Stem Cell Populations. Stem Cell Reports. 4(4):670-84
Liu, Y.C., Couzens, A.L., Deshwar, A.R., B McBroom-Cerajewski, L.D., Zhang, X., Puviindran, V., Scott, I.C., Gingras, A.C., Hui, C.C., Angers, S. (2014) The PPFIA1-PP2A protein complex promotes trafficking of Kif7 to the ciliary tip and Hedgehog signaling. Science signaling. 7:ra117
Nesan, D., Kamkar, M., Burrows, J., Scott, I.C., Marsden, M., Vijayan, M.M. (2012) Glucocorticoid Receptor Signaling Is Essential for Mesoderm Formation and Muscle Development in Zebrafish. Endocrinology. 153(3):1288-1300
Yoruk, B., Gillers, B.S., Chi, N.C., and Scott, I.C. (2012) Ccm3 functions in a manner distinct from Ccm1 and Ccm2 in a zebrafish model of CCM vascular disease. Developmental Biology. 362(2):121-131
Lou, X., Deshwar, A.R., Crump, J.G., and Scott, I.C. (2011) Smarcd3b and Gata5 promote a cardiac progenitor fate in the zebrafish embryo. Development (Cambridge, England). 138(15):3113-23
Lazic, S., and Scott, I.C. (2011) Mef2cb regulates late myocardial cell addition from a second heart field-like population of progenitors in zebrafish. Developmental Biology. 354(1):123-133
Delgado-Olguin, P., Brand-Arzamendi, K., Scott, I.C., Jungblut, B., Stainier, D.Y., Bruneau, B.G., and Recillas-Targa, F. (2011) CTCF Promotes Muscle Differentiation by Modulating the Activity of Myogenic Regulatory Factors. The Journal of biological chemistry. 286(14):12483-94
Chi, N.C., Shaw, R.M., Jungblut, B., Huisken, J., Ferrer, T., Arnaout, R., Scott, I., Beis, D., Xiao, T., Baier, H., Jan, L.Y., Tristani-Firouzi, M., and Stainier, D.Y. (2008) Genetic and Physiologic Dissection of the Vertebrate Cardiac Conduction System. PLoS Biology. 6(5):e109
Davis, J.L., Long, X., Georger, M.A., Scott, I.C., Rich, A., and Miano, J.M. (2008) Expression and comparative genomics of two serum response factor genes in zebrafish. The International journal of developmental biology. 52(4):389-396
Jin, S.W., Herzog, W., Santoro, M.M., Mitchell, T.S., Frantsve, J., Jungblut, B., Beis, D., Scott, I.C., D'Amico, L.A., Ober, E.A., Verkade, H., Field, H.A., Chi, N.C., Wehman, A.M., Baier, H., and Stainier, D.Y. (2007) A transgene-assisted genetic screen identifies essential regulators of vascular development in vertebrate embryos. Developmental Biology. 307(1):29-42
Scott, I.C., Masri, B., D'Amico, L.A., Jin, S.W., Jungblut, B., Wehman, A.M., Baier, H., Audigier, Y., and Stainier, D.Y. (2007) The G protein-coupled receptor agtrl1b regulates early development of myocardial progenitors. Developmental Cell. 12(3):403-413
D'Amico, L., Scott, I.C., Jungblut, B., and Stainier, D.Y. (2007) A Mutation in Zebrafish hmgcr1b Reveals a Role for Isoprenoids in Vertebrate Heart-Tube Formation. Current biology : CB. 17(3):252-259
Beis, D., Bartman, T., Jin, S.W., Scott, I.C., D'Amico, L.A., Ober, E.A., Verkade, H., Frantsve, J., Field, H.A., Wehman, A., Baier, H., Tallafuss, A., Bally-Cuif, L., Chen, J.N., Stainier, D.Y., and Jungblut, B. (2005) Genetic and cellular analyses of zebrafish atrioventricular cushion and valve development. Development (Cambridge, England). 132(18):4193-4204
Scott, I.C. and Stainier, D.Y. (2002) Fishing out a new heart. Science (New York, N.Y.). 298(5601):2141-2142