ZFIN ID: ZDB-PERS-971209-58
Gilmour, Darren
Email: gilmour@embl.de
Affiliation: Neumann Lab, EMBL
Address: Developmental Biology Programme European Molecular Biology Laboratory (EMBL) Meyerhofstrasse 1 Heidelberg, D-69117 Germany
Country: Germany
Phone: 49-7071-601488
Fax: 49-7071-601384

The neural crest provides a population of pluripotent, highly migratory cells which delaminate from the neuroepithelium and differentiate into a wide range of cell types. Neural crest cells originate from the mid- and hindbrain and migrate ventrally to populate the developing head. Once they have reached their targets they differentiate into cartilage, connective tissue, sensory neurons and pigment cells. Although neural crest development has been studied for some time by elegant embryological and in vitro studies very little is known about the genes which regulate this process. As neural crest cells are one of the few vertebate cell types which have no clear analogue in invertebrate species, it is more difficult to apply results from genetic screens in Drosophila and C.elegans to this problem. We are currently using mutants isolated in a large scale zebrafish screen to identify and, eventually, molecularly characterise genes involved in neural crest development in vivo.

During the large screen, 109 mutants, comprising at least 26 genes, were found that affect distinct processes during jaw and branchial arch development. For example, mutations in four genes specifically affect the development of the two anterior arches, whereas other mutations affect only posterior arches. Mutations in about 8 genes affect cartilage differentiation and will be useful in elucidating the distinct regulatory events which underly cartilage formation. We are currently analyzing mutants which show defects in only subsets of arches using a variety of techniques like in situ hybridization, antibody staining, DiI labeling, histological analysis, cell transplantation as well as molecular techniques. As the branchial arches, which are lined by endoderm, become populated by paraxial mesoderm (giving rise to endothelia and pharyngeal muscles) we are also studying how these different tissues interact during the patterning process.

The neural crest cells which arise in the trunk migrate to widely dispersed embryonic locations where they give rise to many differentiated cell fates, such as pigment cells, and neurons and glia of the peripheral nervous system. Although it is a question which has long been considered of some importance, very little is known about the molecules which guide the migrating crest cells and to what extent their final destinations affect their differentiation. We have isolated more than two hundered and eighty mutations, in at least 92 genes, which affect the positioning, differentiation or morphology of pigment cells, a cell type which is derived from the trunk neural crest. We are currently trying to determine to what extent these mutations affect the other crest derived lineages, in the hope that we will find genes which are essential for general neural crest migration and morphogenesis.

Hartmann, J., Wong, M., Gallo, E., Gilmour, D. (2020) An image-based data-driven analysis of cellular architecture in a developing tissue. eLIFE. 9:
Wong, M., Newton, L.R., Hartmann, J., Hennrich, M.L., Wachsmuth, M., Ronchi, P., Guzmán-Herrera, A., Schwab, Y., Gavin, A.C., Gilmour, D. (2020) Dynamic Buffering of Extracellular Chemokine by a Dedicated Scavenger Pathway Enables Robust Adaptation during Directed Tissue Migration. Developmental Cell. 52(4):492-508.e10
Barry, J.D., Donà, E., Gilmour, D., Huber, W. (2016) TimerQuant: A modelling approach to tandem fluorescent timer design and data interpretation for measuring protein turnover in embryos. Development (Cambridge, England). 143(1):174-9
Durdu, S., Iskar, M., Revenu, C., Schieber, N., Kunze, A., Bork, P., Schwab, Y., Gilmour, D. (2014) Luminal signalling links cell communication to tissue architecture during organogenesis. Nature. 515(7525):120-4
Mazaheri, F., Breus, O., Durdu, S., Haas, P., Wittbrodt, J., Gilmour, D., Peri, F. (2014) Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by microglia. Nature communications. 5:4046
Revenu, C., Streichan, S., Donà, E., Lecaudey, V., Hufnagel, L., Gilmour, D. (2014) Quantitative cell polarity imaging defines leader-to-follower transitions during collective migration and the key role of microtubule-dependent adherens junction formation. Development (Cambridge, England). 141:1282-91
Donà, E., Barry, J.D., Valentin, G., Quirin, C., Khmelinskii, A., Kunze, A., Durdu, S., Newton, L.R., Fernandez-Minan, A., Huber, W., Knop, M., and Gilmour, D. (2013) Directional tissue migration through a self-generated chemokine gradient. Nature. 503(7475):285-9
Streichan, S.J., Valentin, G., Gilmour, D., and Hufnagel, L. (2011) Collective cell migration guided by dynamically maintained gradients. Physical Biology. 8(4):045004
Rojas-Muñoz, A., Rajadhyksha, S., Gilmour, D., van Bebber, F., Antos, C., Rodríguez Esteban, C., Nüsslein-Volhard, C., and Izpisúa Belmonte, J.C. (2009) ErbB2 and ErbB3 regulate amputation-induced proliferation and migration during vertebrate regeneration. Developmental Biology. 327(1):177-190
Liu, Y.H., Jakobsen, J.S., Valentin, G., Amarantos, I., Gilmour, D.T., and Furlong, E.E. (2009) A Systematic Analysis of Tinman Function Reveals Eya and JAK-STAT Signaling as Essential Regulators of Muscle Development. Developmental Cell. 16(2):280-291
Lecaudey, V., Cakan-Akdogan, G., Norton, W.H., and Gilmour, D. (2008) Dynamic Fgf signaling couples morphogenesis and migration in the zebrafish lateral line primordium. Development (Cambridge, England). 135(16):2695-2705
Pouthas, F., Girard, P., Lecaudey, V., Ly, T.B., Gilmour, D., Boulin, C., Pepperkok, R., and Reynaud, E.G. (2008) In migrating cells, the Golgi complex and the position of the centrosome depend on geometrical constraints of the substratum. Journal of Cell Science. 121(Pt 14):2406-2414
Valentin, G., Haas, P., and Gilmour, D. (2007) The chemokine SDF1a coordinates tissue migration through the spatially restricted activation of Cxcr7 and Cxcr4b. Current biology : CB. 17(12):1026-1031
Haas, P., and Gilmour, D. (2006) Chemokine signaling mediates self-organizing tissue migration in the zebrafish lateral line. Developmental Cell. 10(5):673-680
Gilmour, D., Knaut, H., Maischein, H.M., and Nüsslein-Volhard, C. (2004) Towing of sensory axons by their migrating target cells in vivo. Nature Neuroscience. 7(5):491-492
Concha, M.L., Russell, C., Regan, J.C., Tawk, M., Sidi, S., Gilmour, D.T., Kapsimali, M., Sumoy, L., Goldstone, K., Amaya, E., Kimelman, D., Nicolson, T., Gründer, S., Gomperts, M., Clarke, J.D.W., and Wilson, S.W. (2003) Local tissue interactions across the dorsal midline of the forebrain establish CNS laterality. Neuron. 39(3):423-438
Gilmour, D.T., Maischein, H.M., Nüsslein-Volhard, C. (2002) Migration and function of a glial subtype in the vertebrate peripheral nervous system. Neuron. 34(4):577-588
Geisler, R., Rauch, G.J., Baier, H., van Bebber, F., Brobeta, L., Dekens, M.P., Finger, K., Fricke, C., Gates, M.A., Geiger, H., Geiger-Rudolph, S., Gilmour, D., Glaser, S., Gnugge, L., Habeck, H., Hingst, K., Holley, S., Keenan, J., Kirn, A., Knaut, H., Lashkari, D., Maderspacher, F., Martyn, U., Neuhauss, S., Neumann, C., Nicolson, T., Pelegri, F., Ray, R., Rick, J.M., Roehl, H., Roeser, T., Schauerte, H.E., Schier, A.F., Schönberger, U., Schönthaler, H.-B., Schulte-Merker, S., Seydler, C., Talbot, W.S., Weiler, C., Nüsslein-Volhard, C., and Haffter, P. (1999) A radiation hybrid map of the zebrafish genome. Nature Genetics. 23(1):86-89