{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:44:41Z","timestamp":1791877481775,"version":"4.3.4"},"reference-count":32,"publisher":"The Company of Biologists","issue":"19","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,10,1]]},"abstract":"<jats:p>Wiskott-Aldrich syndrome protein (WASp) is haematopoietically restricted, and is the causative protein underlying a severe human disorder that can lead to death due to immunodeficiency and haemorrhaging. Much is known about the biochemistry of WASp and the migratory capacity of WASp-defective cells in vitro, but in vivo studies of immune-cell behaviour are more challenging. Using the translucency of zebrafish larvae, we live-imaged the effects of morpholino knockdown of WASp1 (also known as Was) on leukocyte migration in response to a wound. In embryos at 22 hours post-fertilisation, primitive macrophages were impaired in their migration towards laser wounds. Once a circulatory system had developed, at 3 days post-fertilisation, we observed significantly reduced recruitment of neutrophils and macrophages to ventral fin wounds. Cell-tracking studies indicated that fewer leukocytes leave the vessels adjacent to a wound and those that do exhibit impaired navigational capacity. Their cell morphology appears unaltered but their choice of leading-edge pseudopodia is more frequently incorrect, leading to impaired chemotaxis. We also identified two zebrafish mutants in WASp1 by TILLING, one of which was in the WIP-binding domain that is the hotspot for human lesions, and mutants exhibited the same deficiencies in wound inflammation and thrombus formation as WASp1 morphants.<\/jats:p>","DOI":"10.1242\/jcs.032235","type":"journal-article","created":{"date-parts":[[2008,9,10]],"date-time":"2008-09-10T00:44:51Z","timestamp":1221007491000},"page":"3196-3206","source":"Crossref","is-referenced-by-count":76,"title":["Analysis of WASp function during the wound inflammatory response \u2013 live-imaging studies in zebrafish larvae"],"prefix":"10.1242","volume":"121","author":[{"given":"Ana","family":"Cvejic","sequence":"first","affiliation":[{"name":"Departments of Biochemistry and Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK"},{"name":"Department of Haematology, University of Cambridge, Cambridge CB2 2PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Bak-Maier","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Vega","family":"Flores","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil","family":"Crosier","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Redd","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Martin","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042520235461000_REF1","unstructured":"Abramoff, M., Magelhaes, P. and Ram, S. (2004). Image Processing with ImageJ. Biophotonics Int.11, 36-42."},{"key":"2021042520235461000_REF2","doi-asserted-by":"crossref","unstructured":"Andrew, N. and Insall, R. H. (2007). Chemotaxis in shallow gradients is mediated independently of PtdIns 3-kinase by biased choices between random protrusions. Nat. Cell Biol.9, 193-204.","DOI":"10.1038\/ncb1536"},{"key":"2021042520235461000_REF3","doi-asserted-by":"crossref","unstructured":"Brown, S. B., Tucker, C. S., Ford, C., Lee, Y., Dunbar, D. R. and Mullins, J. J. (2007). Class III antiarrhythmic methanesulfonanilides inhibit leukocyte recruitment in zebrafish. J. Leukoc. Biol.82, 79-84.","DOI":"10.1189\/jlb.0107030"},{"key":"2021042520235461000_REF4","doi-asserted-by":"crossref","unstructured":"Calle, Y., Chou, H. C., Thrasher, A. J. and Jones, G. E. (2004). Wiskott-Aldrich syndrome protein and the cytoskeletal dynamics of dendritic cells. J. Pathol.204, 460-469.","DOI":"10.1002\/path.1651"},{"key":"2021042520235461000_REF5","doi-asserted-by":"crossref","unstructured":"Charest, P. G. and Firtel, R. A. (2007). Big roles for small GTPases in the control of directed cell movement. Biochem. J.401, 377-390.","DOI":"10.1042\/BJ20061432"},{"key":"2021042520235461000_REF6","doi-asserted-by":"crossref","unstructured":"Covassin, L., Amigo, J. D., Suzuki, K., Teplyuk, V., Straubhaar, J. and Lawson N. D. (2006). Global analysis of hematopoietic and vascular endothelial gene expression by tissue specific microarray profiling in zebrafish. Dev. Biol.299,551-562.","DOI":"10.1016\/j.ydbio.2006.08.020"},{"key":"2021042520235461000_REF7","doi-asserted-by":"crossref","unstructured":"Falet, H., Hoffmeister, K. M., Neujahr, R. and Hartwig, J. H. (2002). Normal Arp2\/3 complex activation in platelets lacking WASp. Blood100, 2113-2122.","DOI":"10.1182\/blood.V100.6.2113"},{"key":"2021042520235461000_REF8","doi-asserted-by":"crossref","unstructured":"Hall, C., Flores, M., Storm, T., Crosier, K. and Crosier, P. (2007). The zebrafish lysozyme C promoter drives myeloid-specific expression in transgenic fish. BMC Dev. Biol.7, 42.","DOI":"10.1186\/1471-213X-7-42"},{"key":"2021042520235461000_REF9","doi-asserted-by":"crossref","unstructured":"Herbomel, P., Thisse, B. and Thisse, C. (1999). Ontogeny and behaviour of early macrophages in the zebrafish embryo. Development126, 3735-3745.","DOI":"10.1242\/dev.126.17.3735"},{"key":"2021042520235461000_REF10","doi-asserted-by":"crossref","unstructured":"Herbomel, P., Thisse, B. and Thisse, C. (2001). Zebrafish early macrophages colonize cephalic mesenchyme and developing brain, retina, and epidermis through a M-CSF receptor-dependent invasive process. Dev. Biol.238, 274-288.","DOI":"10.1006\/dbio.2001.0393"},{"key":"2021042520235461000_REF11","doi-asserted-by":"crossref","unstructured":"Jin, Y., Mazza, C., Christie, J. R., Giliani, S., Fiorini, M., Mella, P., Gandellini, F., Stewart, D. M., Zhu, Q., Nelson, D. L. et al. (2004). Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype\/genotype correlation. Blood104, 4010-4019.","DOI":"10.1182\/blood-2003-05-1592"},{"key":"2021042520235461000_REF12","doi-asserted-by":"crossref","unstructured":"Lawson, N. D. and Weinstein, B. M. (2002). In vivo imaging of embryonic vascular development using transgenic zebrafish. Dev. Biol.248, 307-318.","DOI":"10.1006\/dbio.2002.0711"},{"key":"2021042520235461000_REF13","unstructured":"Le Guyader, D., Redd, M. J., Colucci-Guyon, E., Murayama, E., Kissa, K., Briolat, V., Mordelet, E., Zapata, A., Shinomiya, H. and Herbomel, P. (2007). Origins and unconventional behavior of neutrophils in developing zebrafish. Blood111, 132-141."},{"key":"2021042520235461000_REF14","doi-asserted-by":"crossref","unstructured":"Lieschke, G. J., Oates, A. C., Crowhurst, M. O., Ward, A. C. and Layton, J. E. (2001). Morphologic and functional characterization of granulocytes and macrophages in embryonic and adult zebrafish. Blood98, 3087-3096.","DOI":"10.1182\/blood.V98.10.3087.h8003087_3087_3096"},{"key":"2021042520235461000_REF15","doi-asserted-by":"crossref","unstructured":"Lutskiy, M. I., Rosen, F. S. and Remold-O'Donnell, E. (2005). Genotype-proteotype linkage in the Wiskott-AlPDFLabdrich syndrome. J. Immunol.175, 1329-1336.","DOI":"10.4049\/jimmunol.175.2.1329"},{"key":"2021042520235461000_REF16","doi-asserted-by":"crossref","unstructured":"Mathias, J. R., Perrin, B. J., Liu, T.-X., Kanki, J., Look, A. T. and Huttenlocher, A. (2006). Resolution of inflammation by retrograde chemotaxis of neutrophils in transgenic zebrafish. J. Leukoc. Biol.80, 1281-1288.","DOI":"10.1189\/jlb.0506346"},{"key":"2021042520235461000_REF17","doi-asserted-by":"crossref","unstructured":"Mathias, J. R., Dodd, M. E., Walters, K. B., Rhodes, J., Kanki, J. P., Look, A. T. and Huttenlocher, A. (2007). Live imaging of chronic inflammation caused by mutation of zebrafish Hai1. J. Cell Sci.120, 3372-3383.","DOI":"10.1242\/jcs.009159"},{"key":"2021042520235461000_REF18","doi-asserted-by":"crossref","unstructured":"Meijer, A. H., van der Sar, A. M., Cunha, C., Lamers, G. E. M., Laplante, M. A., Kikuta, H., Bitter, W. and Becker, T. S. a. S. H. P. (2008). Identification and real-time imaging of a myc-expressing neutrophil population involved in inflammation and mycobacterial granuloma formation in zebrafish. Dev. Comp. Immunol.32, 36-49.","DOI":"10.1016\/j.dci.2007.04.003"},{"key":"2021042520235461000_REF19","doi-asserted-by":"crossref","unstructured":"Ochs, H. D. and Thrasher, A. J. (2006). The Wiskott-Aldrich syndrome. J. Allergy Clin. Immunol.117, 725-738; quiz 739.","DOI":"10.1016\/j.jaci.2006.02.005"},{"key":"2021042520235461000_REF20","doi-asserted-by":"crossref","unstructured":"Pollard, T. D. and Borisy, G. G. (2003). Cellular motility driven by assembly and disassembly of actin filaments. Cell112, 453-465.","DOI":"10.1016\/S0092-8674(03)00120-X"},{"key":"2021042520235461000_REF21","doi-asserted-by":"crossref","unstructured":"Redd, M., Kelly, G., Dunn, G., Way, M. and Martin, P. (2006). Imaging macrophage chemotaxis in vivo: Studies of microtubule function in zebrafish wound inflammation. Cell Motil. Cytoskeleton63, 415-422.","DOI":"10.1002\/cm.20133"},{"key":"2021042520235461000_REF22","doi-asserted-by":"crossref","unstructured":"Renshaw, S. A., Loynes, C. A., Trushell, D. M. I., Elworthy, S., Ingham, P. W. and Whyte, M. K. B. (2006). A transgenic zebrafish model of neutrophilic inflammation. Blood108, 3976-3978.","DOI":"10.1182\/blood-2006-05-024075"},{"key":"2021042520235461000_REF23","doi-asserted-by":"crossref","unstructured":"Ridley, A. J., Schwartz, M. A., Burridge, K., Firtel, R. A., Ginsberg, M. H., Borisy, G., Parsons, J. T. and Horwitz, A. R. (2003). Cell migration: integrating signals from front to back. Science302, 1704-1709.","DOI":"10.1126\/science.1092053"},{"key":"2021042520235461000_REF24","doi-asserted-by":"crossref","unstructured":"Sheehan, H. and Storey, G. (1947). An improved method of staining leukocyte granules with Sudan Black B. J. Pathol. Bacteriol.59, 336.","DOI":"10.1002\/path.1700590142"},{"key":"2021042520235461000_REF25","doi-asserted-by":"crossref","unstructured":"Snapper, S. B., Meelu, P., Nguyen, D., Stockton, B. M., Bozza, P., Alt, F. W., Rosen, F. S., von Andrian, U. H. and Klein, C. (2005). WASP deficiency leads to global defects of directed leukocyte migration in vitro and in vivo. J. Leukoc. Biol.77, 993-998.","DOI":"10.1189\/jlb.0804444"},{"key":"2021042520235461000_REF26","doi-asserted-by":"crossref","unstructured":"Stemple, D. L. (2004). TILLING \u2013 a high-throughput harvest for functional genomics. Nat. Rev. Genet.5, 145-150.","DOI":"10.1038\/nrg1273"},{"key":"2021042520235461000_REF27","doi-asserted-by":"crossref","unstructured":"Takenawa, T. and Suetsugu, S. (2007). The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nat. Rev. Mol. Cell. Biol.8, 37-48.","DOI":"10.1038\/nrm2069"},{"key":"2021042520235461000_REF28","doi-asserted-by":"crossref","unstructured":"Thisse, C., Thisse, B., Schilling, T. F. and Postlethwait, J. H. (1993). Structure of the zebrafish snail1 gene and its expression in wild-type, spadetail and no tail mutant embryos. Development. 119, 1203-1215.","DOI":"10.1242\/dev.119.4.1203"},{"key":"2021042520235461000_REF29","doi-asserted-by":"crossref","unstructured":"Traver, D., Paw, B. H., Poss, K. D., Penberthy, W. T, Lin, S. and Zon, L. I. (2003). Transplantation and in vivo imaging of multilineage engraftment in zebrafish bloodless mutants. Nat. Immunol.4, 1238-1246.","DOI":"10.1038\/ni1007"},{"key":"2021042520235461000_REF30","doi-asserted-by":"crossref","unstructured":"Wienholds, E., van Eeden, F., Kosters, M., Mudde, J., Plasterk, R. H. A. and Cuppen, E. (2003). Efficient target-selected mutagenesis in zebrafish. Genome Res.13, 2700-2707.","DOI":"10.1101\/gr.1725103"},{"key":"2021042520235461000_REF31","doi-asserted-by":"crossref","unstructured":"Wood, W., Faria, C. and Jacinto, A. (2006). Distinct mechanisms regulate hemocyte chemotaxis during development and wound healing in Drosophila melanogaster. J. Cell Biol.173, 405-416.","DOI":"10.1083\/jcb.200508161"},{"key":"2021042520235461000_REF32","doi-asserted-by":"crossref","unstructured":"Zicha, D., Allen, W. E., Brickell, P. M., Kinnon, C., Dunn, G. A., Jones, G. E. and Thrasher, A. J. (1998). Chemotaxis of macrophages is abolished in the Wiskott-Aldrich syndrome. Br. J. Haematol.101, 659-665.","DOI":"10.1046\/j.1365-2141.1998.00767.x"}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/121\/19\/3196\/1504901\/3196.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/121\/19\/3196\/1504901\/3196.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T21:51:18Z","timestamp":1738360278000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/121\/19\/3196\/30330\/Analysis-of-WASp-function-during-the-wound"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,1]]},"references-count":32,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2008,10,1]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.032235","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2008,10,1]]}}}