Professor Kate Storey FRSE
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.
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
Rodrigo Albors, A. and Storey, K. G. (2016) Mapping body-building potential. eLife. 5, e14830
Das, R. M. and Storey, K. G. (2014) Apical abscission alters cell polarity and dismantles the primary cilium during neurogenesis. Science. 343, 200-204
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
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
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
Wilson, V., Olivera-Martinez, I. and Storey, K. G. (2009) Stem cells, signals and vertebrate body axis extension. Development. 136, 1591-1604
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
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
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
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