University of Dundee

Professor Kate Storey FRSE

Neural differentiation in embryos and embryonic stem cells
Position: 
Professor of Neural Development and Head of the Division of Cell and Developmental Biology
Address: 
College of Life Sciences, University of Dundee, Dundee
Full Telephone: 
+44 (0) 1382 385691, int ext 85691
Email: 

Research

Cell division in the neural tubeDuring 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

Contributes lectures to:

 

Human Embryology and Morphology – year 4

Stem Cells in Development and Disease – year 4

Cell & Developmental Biology – year 3​

 

and suprevision for:

Honours student projects – x2 10-week projects

Graduate student seminars/rotation projects – year 1

Publications

Rodrigo Albors, A. and Storey, K. G. (2016) Mapping body-building potential. eLife. 5, e14830
d.o.i 10.7554/eLife.14830
Pubmed: 4798963
PMC: 26949247

Das, R. M. and Storey, K. G. (2014) Apical abscission alters cell polarity and dismantles the primary cilium during neurogenesis. Science. 343, 200-204
d.o.i 10.1126/science.1247521
Pubmed: 4066580
PMC: 24408437

Patel, N. S., Rhinn, M., Semprich, C. I., Halley, P. A., Dolle, P., Bickmore, W. A. and Storey, K. G. (2013) FGF signalling regulates chromatin organisation during neural differentiation via mechanisms that can be uncoupled from transcription. PLoS genetics. 9, e1003614
d.o.i 10.1371/journal.pgen.1003614
Pubmed: 3715432
PMC: 23874217

Olivera-Martinez, I., Harada, H., Halley, P. A. and Storey, K. G. (2012) Loss of FGF-dependent mesoderm identity and rise of endogenous retinoid signalling determine cessation of body axis elongation. PLoS biology. 10, e1001415
d.o.i 10.1371/journal.pbio.1001415
Pubmed: 3484059
PMC: 23118616

Das, R. M. and Storey, K. G. (2012) Mitotic spindle orientation can direct cell fate and bias Notch activity in chick neural tube. EMBO reports. 13, 448-454
d.o.i 10.1038/embor.2012.42
Pubmed: 3343353
PMC: 22491029

Wilson, V., Olivera-Martinez, I. and Storey, K. G. (2009) Stem cells, signals and vertebrate body axis extension. Development. 136, 1591-1604
d.o.i 10.1242/dev.021246
Pubmed: PMC: 19395637

Olivera-Martinez, I. and Storey, K. G. (2007) Wnt signals provide a timing mechanism for the FGF-retinoid differentiation switch during vertebrate body axis extension. Development. 134, 2125-2135
d.o.i 10.1242/dev.000216
Pubmed: PMC: 17507413

Stavridis, M. P., Lunn, J. S., Collins, B. J. and Storey, K. G. (2007) A discrete period of FGF-induced Erk1/2 signalling is required for vertebrate neural specification. Development. 134, 2889-2894
d.o.i 10.1242/dev.02858
Pubmed: PMC: 17660197

Akai, J., Halley, P. A. and Storey, K. G. (2005) FGF-dependent Notch signaling maintains the spinal cord stem zone. Genes & development. 19, 2877-2887
d.o.i 10.1101/gad.357705
Pubmed: 1315394
PMC: 16287717

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 pattern, neuronal differentiation, and segmentation during body axis extension. Neuron. 40, 65-79
d.o.i Pubmed: PMC: 14527434

Brown, J. M. and Storey, K. G. (2000) A region of the vertebrate neural plate in which neighbouring cells can adopt neural or epidermal fates. Current biology : CB. 10, 869-872
d.o.i Pubmed: PMC: 10899008