4 South 0.63
e-mail: bssrnk@bath.ac.uk
Tel: +44 (0) 1225 3828
Anyone interested in opportunities for PhD or post-doctoral study, using zebrafish or medaka, should contact me by e-mail in the first instance.
Current lab members
- Sarah Colanesi
- Jen Greenwood (co-supervised with Dr Phillip Donaghue, University of Bristol)
- Masataka Nikaido
- Frederico Rodrigues
- Marc Sheddon
- Brigite Simoes (co-supervised with Prof. L. Cancela, University of Algarve)
- Laura Vibert
Prof Robert Kelsh
Profile
Current Research
The big picture – neural crest cells as a model of stem cell development and human disease.
We are interested in three fundamental questions in developmental biology: How do multipotent stem cells become specified to one of several distinct fates, how do these specified cells reorganise their gene regulatory network (GRN) to achieve stable differentiation, and how is cell migration through the embryo patterned? These questions are equally important in the related fields of stem cell biology and regenerative medicine, since answering them will help us to understand and control the differentiation of stem cells for therapeutic use, and get them to the correct locations. Likewise, the processes under consideration – maintenance of multipotency, specification of cell fate, genetic control of differentiation, and guided cell migration – are exactly those that are defective in many congenital diseases, so that understanding of the normal process and the disease state, go hand-in-hand.
The vertebrate neural crest is an attractive model system in which to examine all three questions. Neural crest cells are multipotent, forming many diverse cell types, including pigment cells, neurons and glia. Additionally, crest cells undergo extensive migrations and yet form a stereotypic distribution of each cell type within the embryo (Kelsh et al, 2008). Furthermore, understanding crest development has important medical implications since defects in crest development are the basis of many human syndromes, including Waardenburg-Shah syndrome and Hirschsprung's disease, and since neural crest stem cells offer significant promise for therapies (Delfino-Machin et al, 2007).
Zebrafish pigmentation –neural crest development in ‘glorious Technicolor’!
Most, but not all (for example, Carney et al, 2008), of our work focuses on the pigment cells. We use the zebrafish as our model system because the embryo is exquisitely suited to their direct study – the transparency of the embryo makes studying these cells beautifully straight-forward, and the three different pigmented cell-types, all believed to derive from a common progenitor (the chromatoblast), provide a simple model of neural crest development within the neural crest.
My laboratory has experience of the majority of techniques applicable in the zebrafish system. We are currently focusing on developing methods for quantitative modelling of the gene regulatory networks in neural crest cells. We have also developed an innovative in vivo screen for ALK inhibitors (Rodrigues et al, 2012) which we are developing for medium throughput application.
Publications
Yao, S., Cheng, M., Zhang, Q., Wasik, M., Kelsh, R. and Winkler, C., 2013. Anaplastic Lymphoma Kinase is required for neurogenesis in the developing central nervous system of zebrafish. PLoS ONE, 8 (5), e63757.
Gronskov, K., Dooley, C. M., Ostergaard, E., Kelsh, R. N., Hansen, L., Levesque, M. P., Vilhelmsen, K., Mollgard, K., Stemple, D. and Rosenberg, T., 2013. Mutations in C10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism. American Journal of Human Genetics, 92 (3), pp. 415-421.
Kelsh, R. N., 2013. Spotting a role for an Ig superfamily cell adhesion molecule in pigment pattern formation. Pigment Cell & Melanoma Research, 26 (2), pp. 161-162.
Nikaido, M., Law, E. W. P. and Kelsh, R. N., 2013. A systematic survey of expression and function of zebrafish frizzled genes. PLoS ONE, 8 (1), 54833.
Rodrigues, F. S. L. M., Yang, X., Nikaido, M., Liu, Q. and Kelsh, R. N., 2012. A simple, highly visual in vivo screen for anaplastic lymphoma kinase inhibitors. ACS Chemical Biology, 7 (12), pp. 1968-1974.
Rodrigues, F. S. L. M., Doughton, G., Yang, B. and Kelsh, R. N., 2012. A novel transgenic line using the Cre-lox system to allow permanent lineage-labeling of the zebrafish neural crest. Genesis, 50 (10), pp. 750-757.
Breitling, R., Coleing, A., Peixoto, T., Nagle, H., Hancock, E. G., Kelsh, R. N. and Szekely, T., 2012. An overview of the spider fauna of Maio (Cape Verde Islands), with some additional recent records (Arachnida, Araneae). Zoologia Caboverdiana, 2 (2), pp. 43-52.
Strähle, U., Bally-Cuif, L., Kelsh, R., Beis, D., Mione, M., Panula, P., Figueras, A., Gothilf, Y., Brösamle, C., Geisler, R. and Knedlitschek, G., 2012. EuFishBioMed (COST Action BM0804) : a European network to promote the use of small fishes in biomedical research. Zebrafish, 9 (2), pp. 90-93.
Colanesi, S., Taylor, K. L., Temperley, N. D., Lundegaard, P. R., Liu, D., North, T. E., Ishizaki, H., Kelsh, R. N. and Patton, E. E., 2012. Small molecule screening identifies targetable zebrafish pigmentation pathways. Pigment Cell & Melanoma Research, 25 (2), pp. 131-143.
Kelsh, R., 2011. The use of transgenic zebrafish to investigate biological processes in vivo. Transgenic Research, 20 (5), pp. 1150-1151.
Greenhill, E. R., Rocco, A., Vibert, L., Nikaido, M. and Kelsh, R. N., 2011. An iterative genetic and dynamical modelling approach identifies novel features of the gene regulatory network underlying melanocyte development. Plos Genetics, 7 (9), e1002265.
Kelsh, R. N., Szekely, T. and Stuart, S., 2011. Why should biomedical scientists care about biodiversity? Current Biology, 21 (6), R210-R211.
Kelsh, R. N. and Barsh, G. S., 2011. A nervous origin for fish stripes. Plos Genetics, 7 (5), e1002081.
Vibert, L., Nikkaido, M., Greenhill, E. R. and Kelsh, R. N., 2011. A systems biology approach to in vivo dissection of the gene regulatory network (GRN) underlying melanocyte differentiation in zebrafish. Pigment Cell & Melanoma Research, 24 (4), p. 820.
Weiner, A. M. J., Sdrigotti, M. A., Kelsh, R. N. and Calcaterra, N. B., 2011. Deciphering the cellular and molecular roles of cellular nucleic acid binding protein during cranial neural crest development. Development Growth & Differentiation, 53 (8), pp. 934-947.
Taylor, K. L., Lister, J. A., Zeng, Z. Q., Ishizaki, H., Anderson, C., Kelsh, R. N., Jackson, I. J. and Patton, E. E., 2011. Differentiated melanocyte cell division occurs in vivo and is promoted by mutations in Mitf. Development, 138 (16), pp. 3579-3589.
Taylor, K., Richardson, J., Kelsh, R., Jackson, I., Lister, J. and Patton, E. E., 2011. Mitf mutations promote differentiated cell division and melanoma in zebrafish. Pigment Cell & Melanoma Research, 24 (4), p. 797.
Duckworth, J. W., Sebastian, A. C., Kelsh, R. N. and Brandon-Jones, D., 2011. On the apparent occurrence of Hose's Surili Presbytis hosei in Similajau National park, Sarawak, Malaysia. Asian Primate Journal, 2 (1), pp. 29-35.
Kelsh, R. N., 2011. Pigmentation in non-mouse models - fishing for insight, not just horsing around? Pigment Cell & Melanoma Research, 24 (4), p. 772.
Fazenda, C., Simoes, B., Kelsh, R. N., Cancela, M. L. and Conceicao, N., 2010. Dual transcriptional regulation by runx2 of matrix Gla protein in Xenopus laevis. Gene, 450 (1-2), pp. 94-102.
Li, N., Kelsh, R. N., Croucher, P. and Roehl, H. H., 2010. Regulation of neural crest cell fate by the retinoic acid and Pparg signalling pathways. Development, 137 (3), pp. 389-394.
Kelsh, R. N., 2010. The chromatoblast concept - evidence from zebrafish genetics. In: 16th Meeting of the European Society for the Pigment Cell Research (ESPCR), 2010, 2010-09-04 - 2010-09-07, Cambridge.
Kelsh, R. N., Yang, X., Lopes, S. S. and Nikaido, M., 2009. A zebrafish view of progressive fate restriction in neural crest development. Neurogastroenterology & Motility, 21 (2), VIII-VIII.
Dutton, K., Abbas, L., Spencer, J., Brannon, C., Mowbray, C., Nikaido, M., Kelsh, R. N. and Whitfield, T. T., 2009. A zebrafish model for Waardenburg syndrome type IV reveals diverse roles for Sox10 in the otic vesicle. Disease Models & Mechanisms, 2 (1-2), pp. 68-83.
Greenhill, E., Rocco, A., Nikaido, M. and Kelsh, R. N., 2009. Melanocytes, modeling and maths - do we really understand differentiation? Pigment Cell & Melanoma Research, 22 (5), p. 21.
Kelsh, R. N., Harris, M. L., Colanesi, S. and Erickson, C. A., 2009. Stripes and belly-spots : a review of pigment cell morphogenesis in vertebrates. Seminars in Cell & Developmental Biology, 20 (1), pp. 90-104.
Vibert, L., Rocco, A., Nikkaido, M., Greenhill, E. R. and Kelsh, R. N., 2009. Testing in vivo the genetic regulatory network underlying melanocyte differentiation. Mechanisms of Development, 126 (Supplement 1), S316-S317.
Nikaido, M., Yang, X. and Kelsh, R., 2009. Testing the chromatoblast hypothesis in zebrafish neural crest cells by analyzing the fate of cells expressing ltk gene. Mechanisms of Development, 126 (Supplement 1), S96-S97.
Lopes, S. S., Yang, X. Y., Muller, J., Carney, T. J., McAdow, A. R., Rauch, G.-J., Jacoby, A. S., Hurst, L. D., Delfino-Machin, M., Haffter, P., Geisler, R., Johnson, S. L., Ward, A. and Kelsh, R. N., 2008. Leukocyte tyrosine kinase functions in pigment cell development. Plos Genetics, 4 (3), e1000026.
Greenhill, E. R. and Kelsh, R. N., 2008. A pigment evolution Kitlg. Pigment Cell & Melanoma Research, 21 (2), pp. 113-114.
Dutton, J. R., Antonellis, A., Carney, T. J., Rodriguez, F. S. L. M., Pavan, W. J., Ward, A. and Kelsh, R. N., 2008. An evolutionarily conserved intronic region controls the spatiotemporal expression of the transcription factor Sox10. BMC Developmental Biology, 8 (1), p. 105.
Kelsh, R. N. and Greenhill, E., 2008. Experimental analysis of a gene regulatory network underlying zebrafish melanocyte development. Pigment Cell & Melanoma Research, 21 (2), p. 252.
Blentic, A., Tandon, P., Payton, S., Walshe, J., Carney, T., Kelsh, R. N., Mason, I. and Graham, A., 2008. The emergence of ectomesenchyme. Developmental Dynamics, 237 (3), pp. 592-601.
Donoghue, P. C. J., Graham, A. and Kelsh, R. N., 2008. The origin and evolution of the neural crest. Bioessays, 30 (6), pp. 530-541.
