ZFIN ID: ZDB-PERS-970204-5
Wilkinson, David
Email: david.wilkinson@crick.ac.uk
URL: https://www.crick.ac.uk/david-wilkinson
Affiliation: Wilkinson Lab
Address: The Francis Crick Institute, Mill Hill Laboratory The Ridgeway Mill Hill London, NW7 1AA United Kingdom
Country: United Kingdom
Phone: +44 20 8816 2404
Fax: +44-20 8816 2523
ORCID ID: 0000-0001-6757-7080

We investigate molecular mechanisms that control the spatial patterning of cell differentiation and cell migration, using the hindbrain as a simple model. We are analysing how the neural epithelium becomes segmented into regional domains, how subdivisions become refined into a precise organisation of cell types, and how these patterns are stabilised by the control of cell movement. Our work divides into three main areas: (1) Analysis of developmental roles of Eph receptors and ephrins in the control of cell movement, and the mechanisms by which they mediate both cell repulsion and cell adhesion responses; (2) Regulatory networks that control the patterning of neurogenesis, with a current focus on Notch and wnt genes and the formation and functions of boundary cells; (3) Screens and functional analyses of novel genes involved in hindbrain patterning. Most of our work uses the zebrafish system due to its advantages for rapid analysis of gene function, availability of mutants, and in vivo imaging of cell behaviour and transgene expression. In addition, we carry out experiments in chick embryos to compare developmental mechanisms and to use the specific advantages of this system.

David Wilkinson has studied a range of developmental systems. His Ph.D. studies at the University of Leeds were on cell differentiation in Dictyostelium, and postdoctoral research at the Fox Chase Cancer Center, Philadelphia, analysed spatially regulated genes in sea urchin embryogenesis. He then moved to the National Institute for Medical Research, London, where he developed in situ hybridisation methods to study gene expression during mouse development. This work uncovered the spatial expression of the wnt1, FGF3 and Brachyury genes, and led to the discovery of segmental gene expression in the hindbrain (Krox20 and Hox genes). Subsequent gene expression screens in mouse, and functional studies in Xenopus and zebrafish revealed the segmental expression of Eph receptors and ephrins, and their roles in restricting cell movement across boundaries. Recent work has uncovered roles of boundaries in the control of cell differentiation in the zebrafish hindbrain. David Wilkinson is Head of the Division of Developmental Neurobiology, and of the Genetics and Development group of Divisions at the NIMR.

McCallum, S., Obata, Y., Fourli, E., Boeing, S., Peddie, C.J., Xu, Q., Horswell, S., Kelsh, R., Collinson, L., Wilkinson, D., Pin, C., Pachnis, V., Heanue, T.A. (2020) Enteric glia as a source of neural progenitors in adult zebrafish. eLIFE. 9:
Tambalo, M., Mitter, R., Wilkinson, D.G. (2020) A single cell transcriptome atlas of the developing zebrafish hindbrain. Development (Cambridge, England). 147(6):
Thestrup, M.I., Caviglia, S., Cayuso, J., Heyne, R.L.S., Ahmad, R., Hofmeister, W., Satriano, L., Wilkinson, D.G., Andersen, J.B., Ober, E.A. (2019) A morphogenetic EphB/EphrinB code controls hepatopancreatic duct formation. Nature communications. 10:5220
Cayuso, J., Xu, Q., Addison, M., Wilkinson, D.G. (2019) Actomyosin regulation by Eph receptor signaling couples boundary cell formation to border sharpness. eLIFE. 8:
Addison, M., Xu, Q., Cayuso, J., Wilkinson, D.G. (2018) Cell Identity Switching Regulated by Retinoic Acid Signaling Maintains Homogeneous Segments in the Hindbrain. Developmental Cell. 45:606-620.e3
Jacob, J., Ribes, V., Moore, S., Constable, S.C., Sasai, N., Gerety, S.S., Martin, D.J., Sergeant, C.P., Wilkinson, D.G., and Briscoe, J. (2014) Valproic Acid silencing of ascl1b/ascl1 results in the failure of serotonergic differentiation in a zebrafish model of Fetal Valproate Syndrome. Disease models & mechanisms. 7(1):107-17
John, J., Ribes, V., Moore, S., Constable, S., Wilkinson, D., Briscoe, J. (2013) A chemical-genetics approach to study the molecular pathology of central serotonin abnormalities in fetal valproate syndrome. Journal of neurology, neurosurgery, and psychiatry. 84(11):e2
Breau, M.A., Wilkinson, D.G., and Xu, Q. (2013) A Hox gene controls lateral line cell migration by regulating chemokine receptor expression downstream of Wnt signaling. Proceedings of the National Academy of Sciences of the United States of America. 110(42):16892-16897
Gerety, S.S., Breau, M.A., Sasai, N., Xu, Q., Briscoe, J., and Wilkinson, D.G. (2013) An inducible transgene expression system for zebrafish and chick. Development (Cambridge, England). 140(10):2235-2243
Moore, S., Ribes, V., Terriente, J., Wilkinson, D., Relaix, F., Briscoe, J. (2013) Distinct regulatory mechanisms act to establish and maintain Pax3 expression in the developing neural tube. PLoS Genetics. 9:e1003811
Terriente, J., Gerety, S.S., Watanabe-Asaka, T., Gonzalez-Quevedo, R., and Wilkinson, D.G. (2012) Signalling from hindbrain boundaries regulates neuronal clustering that patterns neurogenesis. Development (Cambridge, England). 139(16):2978-2987
Breau, M.A., Wilson, D., Wilkinson, D.G., and Xu, Q. (2012) Chemokine and Fgf signalling act as opposing guidance cues in formation of the lateral line primordium. Development (Cambridge, England). 139(12):2246-2253
Gerety, S.S., and Wilkinson, D.G. (2011) Morpholino artifacts provide pitfalls and reveal a novel role for pro-apoptotic genes in hindbrain boundary development. Developmental Biology. 350(2):279-289
Gonzalez-Quevedo, R., Lee, Y., Poss, K.D., and Wilkinson, D.G. (2010) Neuronal Regulation of the Spatial Patterning of Neurogenesis. Developmental Cell. 18(1):136-147
Sobieszczuk, D.F., Poliakov, A., Xu, Q., and Wilkinson, D.G. (2010) A feedback loop mediated by degradation of an inhibitor is required to initiate neuronal differentiation. Genes & Development. 24(2):206-218
Nikolaou, N., Watanabe-Asaka, T., Gerety, S., Distel, M., Köster, R.W., and Wilkinson, D.G. (2009) Lunatic fringe promotes the lateral inhibition of neurogenesis. Development (Cambridge, England). 136(15):2523-2533
Amoyel, M., Cheng, Y.C., Jiang, Y.J., and Wilkinson, D.G. (2005) Wnt1 regulates neurogenesis and mediates lateral inhibition of boundary cell specification in the zebrafish hindbrain. Development (Cambridge, England). 132(4):775-785
Cheng, Y.C., Amoyel, M., Qiu, X., Jiang, Y.J., Xu, Q., and Wilkinson, D.G. (2004) Notch activation regulates the segregation and differentiation of rhombomere boundary cells in the zebrafish hindbrain. Developmental Cell. 6(4):539-550
Pasini, A., Jiang, Y.J., and Wilkinson, D.G. (2004) Two zebrafish Notch-dependent hairy/Enhancer-of-split-related genes, her6 and her4, are required to maintain the coordination of cyclic gene expression in the presomitic mesoderm. Development (Cambridge, England). 131(7):1529-1541
Pasini, A. and Wilkinson, D.G. (2002) Stabilizing the regionalisation of the developing vertebrate central nervous system. BioEssays : news and reviews in molecular, cellular and developmental biology. 24(5):427-438
Pasini, A., Henrique, D., and Wilkinson, D.G. (2001) The zebrafish Hairy/Enhancer-of-split-related gene her6 is segmentally expressed during the early development of hindbrain and somites. Mechanisms of Development. 100(2):317-321
Xu, Q., Mellitzer, G., and Wilkinson, D.G. (2000) Roles of Eph receptors and ephrins in segmental patterning. Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 355(1399):993-1002
Manzanares, M., Trainor, P.A., Nonchev, S., Ariza-McNaughton, L., Brodie, J., Gould, A., Marshall, H., Morrison, A., Kwan, C.-T., Sham, M.-H., Wilkinson, D.G., and Krumlauf, R. (1999) The role of kreisler in segmentation during hindbrain development. Developmental Biology. 211(2):220-237
Mellitzer, G., Xu, Q., and Wilkinson, D.G. (1999) Eph receptors and ephrins restrict cell intermingling and communication. Nature. 400(6739):77-81
Xu, Q., Mellitzer, G., Robinson, V., and Wilkinson, D.G. (1999) In vivo cell sorting in complementary segmental domains mediated by Eph receptors and ephrins. Nature. 399(6733):267-271
Xu, Q.L., Alldus, G., Macdonald, R., Wilkinson, D.G., and Holder, N. (1996) Function of the Eph-related kinase rtk1 in patterning of the zebrafish forebrain. Nature. 381:319-322
Xu, Q.L., Alldus, G., Holder, N., and Wilkinson, D.G. (1995) Expression of truncated Sek-1 receptor tyrosine kinase disrupts the segmental restriction of gene expression in the Xenopus and zebrafish hindbrain. Development (Cambridge, England). 121:4005-4016

Wilkinson, D.G., Bailes, J.A. and McMahon, A.P. (1987) Expression of the proto-oncogene int-1 is restricted to specific neural cells in the developing mouse embryo. Cell 50, 79-88.

Wilkinson, D.G., Peters, G., Dickson, C. and McMahon, A.P. (1988) Expression of the FGF-related proto-oncogene int-2 during gastrulation and neurulation in the mouse. EMBO J. 7, 691-695.

Wilkinson, D.G., Bhatt, S., Chavrier, P., Bravo, R. and Charnay, P. (1989) Segment-specific expression of a zinc finger gene in the developing nervous system of the mouse. Nature 337, 461-465.

Wilkinson, D.G., Bhatt, S., Cook, M., Boncinelli, E. and Krumlauf, R. (1989) Segmental expression of Hox-2 homoeobox-containing genes in the developing mouse hindbrain. Nature 341, 405-409.

Wilkinson, D.G., Bhatt, S. and Herrmann, B.G. (1990) Expression pattern of the mouse T gene and its role in mesoderm formation. Nature 343, 657-659.

Hunt, P., Gulisano, M., Cook, M., Sham, M.-H., Faiella, A., Wilkinson, D.G., Boncinelli, E. and Krumlauf, R. (1991) A distinct Hox code for the branchial region of the vertebrate head. Nature 353, 861-864.

Nieto, M.A., Bennett, M., Sargent, M. and Wilkinson, D.G. (1992) Cloning and developmental expression of Sna, a murine homologue of the Drosophila snail gene. Development 116, 227-237.

Nieto, M.A., Gilardi-Hebenstreit, P., Charnay, P. and Wilkinson, D.G. (1992) A receptor protein tyrosine kinase implicated in the segmental patterning of the hindbrain and mesoderm. Development 116, 1137-1150.

Nieto, M.A., Sargent, M., Wilkinson, D.G. and Cooke, J. (1994) Control of cell behavior during vertebrate development by Slug, a zinc finger gene. Science 264, 835-839.

Flenniken, A.M., Gale, N.W., Yancopoulos, G.D. and Wilkinson, D.G. (1996) Distinct and overlapping expression of ligands for Eph-related receptor tyrosine kinases during mouse embryogenesis. Dev. Biol. 179, 382-401.

Gale, N.W., Holland, S.J., Valenzuela, D.M., Flenniken, A., Pan, L., Henkemeyer, M., Strebhardt, K., Hirai, H., Wilkinson, D.G., Pawson, T., Davis, S. and Yancopoulos, G.D. (1996) Eph receptors and ligands comprise two major specificity subclasses, and are reciprocally compartmentalised during embryogenesis. Neuron 17, 9-19.

Smith, A., Robinson, V., Patel, K. and Wilkinson, D.G. (1997) The EphA4 and EphB1 receptor tyrosine kinases and ephrin-B2 ligand regulate targeted migration of branchial neural crest cells. Current Biology 7, 561-570.

Theil, T., Frain, M., Gilardi-Hebenstreit, P., Flenniken, A., Charnay, P. and Wilkinson, D.G. (1998) Segmental expression of the EphA4 (Sek-1) receptor tyrosine kinase in the hindbrain is under direct transcriptional control of Krox-20. Development 125, 443-452.

Theil, T., Ariza-McNaughton, L., Manzaneres, M., Brodie, J., Krumlauf, R. and Wilkinson, D.G. (2002) Requirement for downregulation of kreisler during late patterning of the hindbrain. Development 129, 1477-1485.

Coles, E., Christiansen, J., Economou, A., Bronner-Fraser, M. and Wilkinson, D.G. (2004) A vertebrate crossveinless-2 homologue modulates BMP activity and neural crest cell migration. Development 131, 5309-5317.

Poliakov, A., Cotrina, M. and Wilkinson, D.G. (2004) Diverse roles of Eph receptors and ephrins in the regulation of cell migration and tissue assembly. Developmental Cell 7, 465-480.