Department of Biology & Biochemistry
robert_kelsh

Professor of Stem Cell and Developmental Genetics

4 South 0.63

e-mail: r.n.kelsh@bath.ac.uk
Tel: +44 (0) 1225 383828 

 
 

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

  • Dr Deeya Ballim
  • Dr Yusuke Nagao
  • Ruqaiya Al-Jabri
  • Karen Camargo-Sosa
  • Jennifer Owen
  • Kleio Petratou
  • Marc Shedden
 

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?
  • 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; Kelsh and Erickson, 2013). 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’!

We focus largely on neural crest-derived pigment cells as a highly tractable ‘model-within-a-model’ (Lapedriza et al, 2014; Schartl et al, 2016), but also are looking at neuronal derivatives (e.g. Elworthy et al., 2005; Carney et al., 2008; Delfino-Machin et al., 2017). 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.

We are studying the fundamental issue of how stem cells function – does fate choice follow a Direct Fate Restriction or Progressive Fate Restriction Model – and aim to reconcile these two conflicting views of neural crest development. We are using classic genetics, single cell transcriptional profiling and various mathematical modelling approaches to understand how GRNs reorganise to allow selection of alternative fate choices (Greenhill et al., 2011; Nagao et al., 2014; Vibert et al., 2017; Nagao et al., in prep.; Subkhankulova et al., in prep.). We are using genetics, clonal analysis and imaging to understand larval pigment pattern formation and the mechanisms driving adult pigment stem cell segregation and quiescence (Camargo-Sosa et al., in prep.). Finally, we are using the zebrafish mutants to model human disease, currently focusing on understanding genotype-phenotype correlations in SOX10-associated conditions.

My laboratory has experience of the majority of techniques applicable in the zebrafish system. More advanced techniques that we are currently developing/utilising include single cell transcriptomics, Cre-lox recombination for clonal analysis, mathematical modelling of both GRNs and pigment pattern formation, and high efficiency phenotypic rescue using microinjection.

Publications

Awasthi Mishra, N., Droegemueller, C., Jagannathan, V., Keller, I., Wuthrich, D., Bruggmann, R., Beck, J., Schuetz, E., Brenig, B., Demmel, S., Moser, S., Signer-Hasler, H., Pienkowska-Schelling, A., Schelling, C., Sande, M., Rongen, R., Rieder, S., Kelsh, R. N., Mercader, N. and Leeb, T., 2017. A structural variant in the 5′-flanking region of the TWIST2 gene affects melanocyte development in belted cattle. PLoS ONE, 12 (6), e0180170.

Kelsh, R. N. and Petratou, K., 2017. Gnawing at striping - how rodents evolve striped patterns. Pigment Cell & Melanoma Research, 30 (2), pp. 181-182.

Delfino-Machin, M., Madelaine, R., Buscolin, G., Nikaido, M., Colanesi, S., Camargo Sosa, K., Law, E. W. P., Toppo, S., Blader, P., Tiso, N. and Kelsh, R. N., 2017. Sox10 contributes to the balance of fate choice in dorsal root ganglion progenitors. PLoS ONE, 12 (3), e0172947.

Vibert, L., Aquino, G., Gehring, I., Subkhankulova, T., Schilling, T. F., Rocco, A. and Kelsh, R., 2017. An ongoing role for Wnt signaling in differentiating melanocytes in vivo. Pigment Cell & Melanoma Research, 30 (2), pp. 219-232.

Kelsh, R., Camargo Sosa, K., Owen, J. and Yates, C., 2017. Zebrafish adult pigment stem cells are multipotent and form pigment cells by a progressive fate restriction process. Bioessays, 39 (3), 1600234.

Guillot, R., Muriach, B., Rocha, A., Rotllant, J., Kelsh, R. and Cerda-Reverter, J. M., 2016. Thyroid hormones regulate zebrafish melanogenesis in a gender-specific manner. PLoS ONE, 11 (11), e0166152.

Lee, E. M., Yuan, T., Ballim, R. D., Nguyen, K., Kelsh, R. N., Medeiros, D. M. and McCauley, D. W., 2016. Functional constraints on SoxE proteins in neural crest development: the importance of differential expression for evolution of protein activity. Developmental Biology, 418 (1), pp. 166-178.

Arnheiter, H., Long, G., Aplin, A., Harris, J. and Kelsh, R., 2016. Triple jeopardy for people with albinism. Pigment Cell & Melanoma Research, 29 (5), p. 487.

Ando, K., Fukuhara, S., Izumi, N., Nakajima, H., Fukui, H., Kelsh, R. N. and Mochizuki, N., 2016. Clarification of mural cell coverage of vascular endothelial cells by live imaging of zebrafish. Development, 143 (8), pp. 1328-1339.

Argüelles Ticó, A., Kupper, C., Kelsh, R. N., Kosztolányi, A., Szekely, T. and van Dijk, R. E., 2016. Geographic variation in breeding system and environment predicts melanin-based plumage ornamentation of male and female Kentish plovers. Behavioral Ecology and Sociobiology, 70 (1), pp. 49-60.

Arnheiter, H., Long, G., Aplin, A., Harris, J. and Kelsh, R., 2016. Welcome to the New Year! Pigment Cell & Melanoma Research, 29 (1), p. 3.

Schartl, M., Larue, L., Goda, M., Bosenberg, M. W., Hashimoto, H. and Kelsh, R. N., 2016. What is a vertebrate pigment cell? Pigment Cell & Melanoma Research, 29 (1), pp. 8-14.

Cerda-Reverter, J., Rotllant, J. and Kelsh, R., 2015. Spots, not stripes, from just holding on. Pigment Cell & Melanoma Research

Arnheiter, H., Bosenberg, M., Aplin, A. and Kelsh, R., 2015. The value of thesis advisers. Pigment Cell & Melanoma Research, 28 (4), p. 371.

Kelsh, R., Aplin, A., Arnheiter, H. and Bosenberg, M., 2015. Animal experimentation--questioned again! Pigment Cell & Melanoma Research, 28 (3), p. 241.

Ceinos, R. M., Guillot, R., Kelsh, R. N., Cerda-Reverter, J. M. and Rotllant, J., 2015. Pigment patterns in adult fish result from superimposition of two largely independent pigmentation mechanisms. Pigment Cell & Melanoma Research, 28 (2), pp. 196-209.

Simões, B., Conceição, N., Matias, A. C., Bragança, J., Kelsh, R. N. and Cancela, M. L., 2015. Molecular characterization of cbfβ gene and identification of new transcription variants:Implications for function. Archives of Biochemistry and Biophysics, 567, pp. 1-12.

Kelsh, R., Kos, L., Arnheiter, H., Aplin, A. and Bosenberg, M., 2015. What shall we do this year? Pigment Cell & Melanoma Research, 28 (1), p. 1.

Nagao, Y., Takada, H., Seki, R., Kamei, Y., Hara, I., Taniguchi, Y., Naruse, K., Hibi, M., Kelsh, R. N. and Hashimoto, H., 2015. Forthcoming. Roles of sox10 and its possible interaction with sox5 in pigment cell development. Pigment Cell & Melanoma Research

Aplin, A., Bosenberg, M., Soengas, M., Kos, L., Arnheiter, H. and Kelsh, R., 2014. Unmet needs in melanoma research. Pigment Cell & Melanoma Research, 27 (6), p. 1003.

Bosenberg, M., Arnheiter, H. and Kelsh, R., 2014. The world of pigment cell research. Pigment Cell & Melanoma Research, 27 (5), p. 683.

Simoes, B., Conceição, N., Kelsh, R. and Cancela, M. L., 2014. Identification of cis-regulatory elements in the upstream regions of zebrafish runx3 gene through an in silico analysis:Implications for function. Journal of Applied Ichthyology, 30 (4), pp. 661-670.

Kelsh, R., 2014. Thank you Pernille! Pigment Cell & Melanoma Research, 27 (4), 505 - 506.

Montoliu, L. and Kelsh, R., 2014. Do you have to be albino to be albino? Pigment Cell & Melanoma Research, 27 (3), pp. 325-326.

Nagao, Y., Suzuki, T., Shimizu, A., Kimura, T., Seki, R., Adachi, T., Inoue, C., Omae, Y., Kamei, Y., Hara, I., Taniguchi, Y., Naruse, K., Wakamatsu, Y., Kelsh, R. N., Hibi, M. and Hashimoto, H., 2014. Sox5 Functions as a Fate Switch in Medaka Pigment Cell Development. Plos Genetics, 10 (4), e1004246.

Lapedriza, A. and Kelsh, R. N., 2014. Reflecting on the iridophore transcriptome, and more. Pigment Cell & Melanoma Research, 27 (1), 2–3.

Lapedriza, A., Petratou, K. and Kelsh, R. N., 2014. Neural Crest Cells and Pigmentation. In: Trainor, P., ed. Neural Crest Cells.1st ed. Boston, U. S. A.: Academic Press, pp. 287-311.

Kelsh, R., 2013. Functional nasal morphology of chimaerid fishes. Journal of Morphology, 274 (9), pp. 987-1009.

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.

Kelsh, R., 2013. Towards a quantitative model of the gene regulatory network underlying melanocyte development. In: International Pigment Cell Development Workshop, 2013-05-20 - 2015-07-24.

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.

Kelsh, R., 2013. Mutations in C10orf11, encoding a melanocyte differentiation gene, cause autosomal recessive albinism. Pigment Cell & Melanoma Research, 26 (5), E25.

Kelsh, R. N. and Erickson, C. A., 2013. Neural crest:origin, migration and differentiation. eLS

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.

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.

This list was generated on Wed Sep 20 13:42:54 2017 IST.

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