Professor Kim DaleFRSB

The broad interest of the laboratory aims to further our understanding of how several genetic interactions come into play at the earliest stages of development to build the developing embryo.

Segmentation is a universal feature of the body plan of all vertebrate species. This is most clearly seen in the vertebrate axial skeleton which is comprised of a series of segments, namely the ribs and articulating vertebrae. In vertebrate species the process of segmentation begins with the sequential formation of structures called somites, which later develop into the ribs and vertebrae. Interference with this process of somitogenesis can lead to serious segmental defects and associated pathologies, such as Spondylocostal dysostosis (SCD). The aetiology of most Abnormal vertebral segmentation (AVS) Syndromes is unknown. However, one signalling pathway that has been associated with several human disorders such as SCD is the Notch signalling pathway. Somitogenesis is regulated by a molecular oscillator which drives oscillating gene expression in the paraxial mesoderm from which somites arise. The key components of the segmentation clock are intracellular components of the Notch, Wnt and FGF pathways. We have shown in mouse and chick, Notch activity is essential for both dynamic expression of all clock genes and for somite formation. Outstanding questions in the field which we are addressing are as follows:

1. Oscillating genes are negative regulators of the pathways which activate them. It seems clear how these negative feedback loops regulate oscillatory gene expression intracellularly. We are investigating how patterns of gene expression are propagated across the PSM.
2. How is the pace of the clock gene oscillations regulated?
3. What is the level of cross talk and hierarchy within and between the Notch, Wnt and FGF pathways within the molecular oscillator.

Selected Publications

1. Dale JK, Maroto M, Dequeant M-L, Malapert P, McGrew M, Pourquie O. (2003) Periodic inhibition by Lunatic Fringe underlies the chick Segmentation Clock. Nature 16; 421(6920):275-8.
2. Ferjentsik Z, Hayashi S*, Dale JK*, Bessho Y, Herreman A, De Strooper B, del Monte G, Pompa JL, Maroto M (2009). Notch is a critical component of the mouse somitogenesis oscillator and is essential for the formation of the somites. PLOS Genetics; 5(9):e1000662. *Joint second authors.
3. Gray S and Dale JK. (2010) Notch signalling regulates contribution of progenitor cells from chick Hensen’s node to the floor plate and notochord. Development. 137(4):561-8
4. Bone R, Bailey C, Wiedermann G, Ferjentsik Z, Appleton P, Murray P, Maroto M, Dale JK (2014) Spatio-temporal oscillations of the Notch1, Dll1 ligand and NICD are coordinated across the mouse PSM. Development 141:4806-4816
5. Stasiulewicz M, Gray S, Mastromina I, Silva JC, Bjorklund M, Seymour PA, Booth D, Thompson C, Green R, Hall EA, Serup P, Dale JK. (2015) A conserved role for Notch in priming the cellular response to Shh through ciliary localisation of the key Shh transducer, Smo. Development. 2015 Jul 1;142(13):2291-303
6. Wiedermann G, Bone R, Clara J, Bjorklund M, Murray P, and Dale JK. (2015) A balance of positive and negative regulators determines the pace of the segmentation clock. eLife 2015;10.7554/eLife.05842
7. Ioanna Mastromina, Laure Verrier, Kate G. Storey, J. Kim Dale. (2018) MYC activity is required for maintenance of the neuromesodermal progenitor signalling network and for segmentation clock gene oscillations in mouse. Development. 2018 Jul 30;145(14). pii: dev161091. doi: 10.1242/dev.161091.
8. Francesca Anna Carrieri, Philip Murray, Dimitra Ditsova, Ferris MA, Paul Davies, J. Kim Dale (2019) CDK1 and CDK2 regulate NICD1 turnover and the periodicity of the segmentation clock EMBO Rep. 2019 Apr 17. pii: e46436. doi: 10.15252/embr.201846436
9. Fay Cooper, Celine Souilhol Scott Haston , Shona Gray, Katy Boswell, Antigoni Gogolou, Frith T, Stavish D, Jasmes B, Bose D, Dale J.K., Tskaraidis A. (2024) Notch signalling influences cell fate decisions and HOX gene induction in axial progenitors Development 1;151(3):dev202098. doi:10.1242/dev.202098. Epub 2024 Feb 12.
10. French, M., Portero Migueles, R., Dale, K., Blin, G., Wilson, V. & Lowell, S. (2024), A toolkit for mapping cell identities in relation to neighbours reveals Notch-dependent heterogeneity within neuromesodermal progenitor populations (Accepted/In press) In: PLoS Biology. bioRxiv
11. H.Meijer, S. Johnson, L. Davidson, A. Hetherington, P. Murray, P. Davies, J. K. Dale (under review) Notch1 S2513 is critical for the regulation of NICD levels in hiPSC derived PSM cells and somite formation. bioRxiv

People in my lab

• Dr Hedda Meijer (Postdoctoral Researcher)
• Dr Sara Johnson (Postdoctoral Researcher)
• Adam Hetherington (Technician)
• Rosie Gallagher (PhD student - second supervisor)

• Lectures: Cell & Developmental Biology Master’s year
• Supervision of two UG Hons students annually for their honours project
• Supervision of one MSc student annually for their research project

D'Arcy Thompson Unit Divisional Representative for the MRC Protein Phosphorylation and Ubiquitylation Unit.