Kate Storey

Professor Kate Storey

Position: Professor of Neural Development and Head of the Division of Cell and Developmental Biology
Division: Cell and Developmental Biology
Address: College of Life Sciences, University of Dundee, Dundee
Telephone: +44 1382 385828, int ext. 85691
Fax: +44 1382 385386
Email: k.g.storey@dundee.ac.uk
Website: Storey Lab

Neural differentiation in embryos and embryonic stem cells

Research

Cell division in the neural tube During development cells have to become different from each other, acquiring particular characteristics in appropriate positions in the embryo. We focus on how cells acquire a neural fate and on the mechanisms that determine what type of nerve cell will form and when it will differentiate. We are using combinations of cellular and molecular techniques to investigate these processes mainly in the early chick embryo and most recently in mouse Embryonic Stem (ES) cells.


The spinal cord is generated over an extended period of time in a head to tail sequence and so is ideal for studying the temporal sequence of events that control neural differentiation. A group of cells at the tail end of embryo divide in a stem cell mode to give rise to the entire spinal cord. These stem zone cells remain in an undifferentiated state, but once cells leave this region they are able to turn on neuronal differentiation and patterning genes and some cells exit the cell cycle.We have found that the changing signalling properties of neighbouring paraxial mesoderm control differentiation onset in the extending neural axis and have identified two signalling pathways that work in opposition to control this step; Fibroblast Growth Factor (FGF) signalling maintains the undifferentiated state of the stem zone, while Retinoic acid (RA, a derivative of vitamin A) provided by segmenting mesoderm (somites) inhibits FGF signalling and drives neuron production and patterning. This FGF/RA switch appears to be a conserved differentiation event that can be identified in other embryonic tissues and is also aberrant in many cancer cell lines.


Current projects in laboratory address: i) the interaction of FGF and RA pathways, their interaction with further key signalling pathways and their regulation of cell cycle and differentiation genes; ii) cell behaviour and signalling dynamics during neurogenesis, using real- time imaging techniques; iii) regulation of neural differentiation in embryonic stem cells.


The overall aim of our work is to establish fundamental signalling networks and relationships which govern the differentiation status and behaviour of cells in the newly generated neural axis and to use these insights to investigate the molecular mechanisms that direct stable differentiation of ES cells.

Teaching

Developmental Biology (3rd year)
4 lectures: Human embryonic development; Neural induction; Neural patterning; Wiring the nervous system
Vertebrate Embryology practical class (alternate years)

Publications


  1. Das, R.M., Wilcock, A.C., Swedlow, J.R. and Storey, K.G.  High resolution live imaging of cell behaviour in the developing neuroepithelium  J. Vis. Exp. (Not Set) e3920. DOI: 10.3791/3920 (2011).

  2. Vilas-Boas, F., Fior, R., Swedlow, J.R., Storey, K.G. and Henrique, D. (2011) A novel Reporter of Notch Signaling indicates regulated and random Notch Activation during Vertebrate Neurogenesis.  BMC Biology  9.58.

  3.  Martinez-Morales, P.L., Diez del Corral, R., Olivera-Martinez, I., Quiroga, A.C., Das, R.M., Barbas, J.A., Storey, K.G. and Morales, A.V. (2011) FGF and RA activity gradients control the timing of neural crest cell emigration in the trunk.  J. Cell Biol. 194(3), 489-503..

  4. Bouskila, M., Esoof, N., Gay, L., Fang, E.H., Deak, M., Begley, M., Cantley, L.C., Prescott, A., Storey, K.G., Alessi, D.R. (2011) TTBK2 substrate specificity and the impact of spinocerebellar ataxia-causing mutations on kinase activity, localisation and development, Biochem. J. 437,157-67.

  5. Shiau, C.E., Das, R.M. and Storey, K.G. (2011) An effective assay for high cellular resolution time-lapse imaging of neurogenic placode formation and morphogenesis.  BMC Neuroscience 12, 37.

  6. LI, R.A., Storey, K.G. (2011) An emerging molecular mechanism for the neural vs mesodermal cell fate decision. Cell Res. 21(5), 708-710.

  7. Stavridis, M.P., Collins, B.J. andStorey, K.G (2010). Retinoic acid orchestrates fibroblast frowth factor signalling to drive embryonic stem cell differentiation Development 137(6), 881-890.

  8. Fishwick, K.J., Li, R.A., Deng, P., Halley, P. Deng, P.Y. and Storey, K.G (2010). Initiation of neuronal differentiation requires PI3-kinase/TOR signalling in the vertebrate neural tube. Developmental Biology 338(2), 215-225.

  9. Wilson, V., Olivera-Martinez, I. and Storey, K.G. (2009). Stem cells, signals and vertebrate body axis extension. Development 136, 1591-1604.

  10. Ekerot, M., Stavridis, M.P., Delavaine, L., Mitchell, M.P., Staples, C., Owens, D.M., Kennan, I.D., Dickinson, R.J., Storey, K.G. and Keyse, S.M. (2008). Negative-feedback regulation of FGF signalling by DUSP6/MKP-3 is driven by ERK1/2 and mediated by Ets factor binding to a conserved site within the DUSP6/MKP-3 gene promoter. Biochem J. 2, 287-98.

  11. Stavridis, M.S., Lunn, J.S., Collins, B.J. and Storey, K.G. (2007).  A discrete period of FGF/Erk1/2 activity is required for vertebrate neural specification.  Development 134, 2889-2894.

  12. Olivera-Martinez, I.M. and Storey, K.G. (2007).  Wnt signals provide a timing mechanism for the FGF/Retinoid differentiation switch in the early spinal cord.  Development 134, 2125-2135.  

  13. Wilcock, A.C., Swedlow, J.R. and Storey, K.G. (2007).  Mitotic spindle orientation distinguishes stem cell and terminal modes of neuron production in the early spinal cord.  Development 134, 1943-1954.

  14. Lunn, J.S., Fishwick, K.J., Halley, P.A. and Storey, K.G. (2007).  A spatial and temporal map of FGF/Erl1/2 activity and response repertoires in the early chick embryo.  Developmental Biology 302, 536-552.

  15. Das, R.M., Van Hateren, N.J., Howell, G.R., Farrell, E.R., Bangs, F., Porteous, V.C., Manning, E.M., McGrew, M.J., Ohyama, K., Sacco, M.A., Halley, P.A., Sang, H.M., Storey, K.G., Placzek, M., Tickle, C., Nair, V.K. and Wilson, S.A. (2006).  A robust system for RNA interference in the chicken using a modified microRNA operon.  Developmental Biology 294, 554-563.

  16. Akai, J., Halley, P.A. and Storey, K.G. (2005).  FGF dependent Notch signalling maintains the spinal cord stem zone.  Genes and Development 132, 2877-2887.

  17. Delfino-Machin, M., Lunn, J.S., Breitkreuz, D.N., Akai, J. and Storey, K.G. (2005).  Specification and maintenance of the spinal cord stem zone.  Development 132 4273-4283. 

  18. Diez del Corral, R., Olivera-Martinez, I., Goriely, A., Gale, E., Maden, M. and Storey, K.G. (2003).  Opposing FGF and Retinoid pathways: a signalling switch that controls differentiation and patterning onset in the extending vertebrate body axis extension.  Bioessays Aug 26; (8): 857-869.

  19. Diez del Corral, R., Olivera-Martinez, I., Goriely, A., Gale, E., Maden, M. and Storey, K.  (2003).  Opposing FGF and Retinoid pathways control ventral neural patterning, neuronal differentiation and segmentation during body axis extension.  Neuron 40, 65-79.

  20. Eblaghie, M., Lunn, J.S., Dickinson, R., Munsterberg, A.E., Sanz-Ezquerro, J-J., Farrell, E.R., Mathers, J., Keyse, S.M., Storey, K. and Tickle, C. (2003).  Negative feedback regulation of FGF signalling levels by Pyst1/MKP3 in chick embryos.  Current Biology 13, 1009-1018.

Awards

  • Fellow of the Society of Biology (2011)
  • Fellow of the Royal Society of Arts (2011)