Position: Royal Society University Research Fellow
Division: Cell and Developmental Biology
Address: College of Life Sciences,
University of Dundee,
Dundee
Telephone: +44 1382 386290, int ext. 86290
Fax: +44 1382 385386
Email: j.k.dale@dundee.ac.uk
Website: Dale Lab Group
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. Primitive streak formation is reputed as being `the most important time in ones life' since it generates the three germ layers of the embryo proper. The progenitor cells of these three germ layers ingress into the primitive streak where they form a resident population of stem cells for each tissue type. One main focus of the laboratory will be to gain a deeper understanding of the mechanism of regulation of these stem cells both in the mouse and the chick system. We will initially try to identify the location of the stem cell pools. We will then investigate the function of potential candidate signalling pathways involved in maintaining this stem cell state.
The laboratory will focus on the role of the Notch signalling pathway in the development of three primitive streak derived axial tissues; namely the ventral neural tube and the underlying axial mesoderm of the notochord and prechordal mesoderm. These three tissues are believed to share a common precursor in the primitive streak. As they leave the streak they become regionalised along the anteroposterior axis as judged by the expression of regionalised markers. We will investigate whether periodic Notch activity in the primitive streak provides a counting mechanism implicated in anteroposterior axis regionalisation.
We also aim to investigate the role of Notch signalling during specification of these three tissue types. Despite being co-expressed in a periodic fashion in the primitive streak precursors, Notch target genes become differentially expressed in axial mesoderm and the ventral neural tube as these tissues leave the primitive streak and differentiate. We shall investigate whether differential Notch target gene expression introduces a 'bias' in cell fate specification.
1. Winzi M, Hyttel P, Dale K, Serup P (2011) Isolation and Characterization of Node/Notochord-like Cells from Mouse Embryonic Stem Cells. Stem Cells and Development (ahead of print doi:10.1089/scd.2011.0042).
2. Terry AJ, Sturrock M, Dale JK, Maroto M, Chaplian MAJ (2011) A Spatio-Temporal Model of Notch Signalling in the Zebrafish Segmentation Clock: Conditions for Synchronised Oscillatory Dynamics PLoS ONE 6(2): e16980. doi:10.1371/journal.pone.0016980.
3. Gibb S, Maroto M, Dale JK (2010) The integration of signalling events during somitogensis. Trends in cll Biology. 20(10) 593-600.
4. 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.
5. Wright D, Ferjentsik Z, Qiu X, Jiang YJ, Van Hateren N, Wilson SA, Malapert P, Pourquie O, Dale JK, Maroto M (2009) Cyclic Nrarp mRNA expression is regulated by the somitic oscillator but Nrarp protein levels do not oscillate. Dev. Dynamics 238(12):3043-55.
6. 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.
7. Hayashi S, Shimoda T, Nakajima M, Tsukada Y, Sakumura Y, Dale JK, Maroto M, Kohno K, Matsui T, Bessho Y (2009) Sprouty4, an FGF inhibitor, displays cyclic gene expression under the control of the Notch segmentation clock in the mouse PSM PLOS One;4(5):e5603.
8. Gibb S, Zagorska A, Melton K, Tenin G, Vacca I, Trainor P, Maroto M, and Dale JK (2009). Interfering with Wnt signalling alters the Periodicity of the Segmentation Clock. Developmental Biology 330(1):21-31.
9. Dale JK, Malapert P, Chal J, Vilhais-Neto G, Maroto M, Johnson T, Jayasinghe S, Trainor P, Herrmann B, Pourquie O. (2006) Oscillations of the snail genes in the presomitic mesoderm coordinate segmental patterning and morphogenesis in vertebrate somitogenesis. Developmental Cell10(3):355-66.
10. Maroto M, Dale JK, Dequeant ML, Petit AC, Pourquie O. (2005) Synchronized cycling gene oscillations in PSM cells require cell-cell contact. Int. J. Dev. Biol. 49 (2-3):309-315.
11. Dale JK and Maroto M. (2003) A Hes1-based oscillator in cultured cells and its potential implications for the Segmentation Clock. Bioessays 25: 200-203.
12. 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.
13. Leimaster C, Dale K, FischerA, Klamt B, Hrabe de Angelis M, Radtke F, McGrew M, Pourquie O, Gessler M.(2000). Oscillating expression of c-Hey2 in the presomitic mesoderm suggests that the segmentation clock may use combinatorial signalling through multiple interacting bHLHfactors. Developmental Biology 226: 91-103.
14. Dale JK and Pourquie O. (2000). A clock-work somite. Bioessays 22: 72-83.
15. Dale JK, Sattar N, Heemskerk J, Clarke JD, Placzek M, Dodd J. (1999). Differential patterning of ventral midline cells by axial mesoderm is regulated by BMP7 and chordin. Development 126 (2): 397-408.
16. McGrew MJ, Dale JK, Fraboulet S, Pourquie O. (1998). The lunatic fringe gene is a target of the molecular clock linked to somite segmentation in avian embryos. Current Biology 8 (17): 979-82.
17. Dale JK, Vesque C, Lints TJ, Sampath TK, Furley A, Dodd J, Placzek M. (1997). Cooperation of BMP7 & SHH in the induction of forebrain ventral midline cells by prechordal mesoderm. Cell 90 (2): 257-69.
Book Chapters & Reviews
1. Palmerim I, Rodrigues S, Dale JK, Maroto M (2008). Development on time. In “Cellular Oscillatory Mechanisms”, pp 62-68. Maroto M & Monk N eds. Austin/New York. Landes Bioscience/Springer.
2. Maroto M, Iimura T, Dale JK, Bessho Y. (2008). bHLH proteins and their role in somitogenesis. In “Somitogenesis”, pp 124-139. Maroto M & Whittock NV, eds. Austin/New York. Landes Bioscience/Springer.
3. Pourquie Olivier , Dale K, Dubrulle J, Jouve C, Maroto M and McGrew M. (2001) A molecular clock linked to vertebrate segmentation. The origin and fate of somites Sanders EJ Lash JW, and Ordahl. (IOS press), pp. 64-70.
4. Gibb S, Maroto M, Dale JK. (2010) The segmentation clock mechanism moves up a notch. Trends in Cell Biology 20(10):593-601
