Our research exploits genetic strategies to identify the key signalling cues and downstream transcriptional regulators that mediate cell fate decisions in the developing mouse embryo. We want to understand how the information encoded in our genomes – both the protein coding information and the cis-regulatory elements underpinning precise temporal and spatial control – drives growth and morphogenesis of the early post-implantation embryo to generate both the embryo proper as well as the all-important extra-embryonic lineages that collaborate with the maternal uterine tissues to form the placenta necessary to sustain development of the embryo.
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Our major contribution has been the discovery that the intersection of the TGFb growth factors Nodal and BMPs orchestrate early axis formation and specification of the germ layers and germ cells. For example we’ve shown that combinatorial Nodal and BMP signalling regulates the size of the germ cell niche and hence the number of epiblast cells that induce expression of the BMP target gene Blimp1 to specify precursor PGCs that give rise to the mammalian germ line.
Our current interest is investigating how the T-box transcription factor Eomesodermin functions downstream of Nodal/Smad2 to both orchestrate cell fate allocation during gastrulation, and govern trophoblast stem cell maintenance. Using a combination of in vivo fate mapping together with in directed in vitro differentiation protocols we have uncovered an essential role for Eomes in both specification of the cardiovascular progenitors, as well as in regulating competence of the extra-embryonic mesoderm of the yolk sac to give rise to the two initial waves of blood cell formation. We are currently exploiting degron tagging approaches, in combination with single cell genomics, to more precisely delineate Eomes functions as a key lineage specifying transcription factor during gastrulation as well as exploring its roles in the trophoblast of the developing placenta.
2021
The T-box Transcription Factor Eomesodermin Governs Hemogenic Competence of Yolk Sac Mesodermal Progenitors.
Harland, L.T.G., Simon, C.S., Senft, A.D., Costello, I., Greder L., Imaz-Rosshandler, I., Gottgens, B., Marioni, J.C., Bikoff, E.K., Porcher, C., de Bruijn, M. and Robertson, E.J.
Nature Cell Biology – 23(1): 61-74.
2020
The transcriptional repressor Blimp1/PRDM1 regulates the maternal decidual response in mice.
Goolam, M., Xypolita, M-L., Costello, I., Lydon, J., De Mayo, F., Bikoff, E.K., Robertson, E.J. and Mould, A.W.
Nature Communications – 11(1): 2782.
2019
Genetic dissection of Nodal and Bmp signalling requirements during primordial germ cell development in mouse.
Senft, A., Bikoff, E.K., Robertson, E.J. and Costello, I.
Nature Communications – 10(1): 1089.
2018
Combinatorial Smad2/3 Activities Downstream of Nodal Signaling Maintain Embryonic/Extra-Embryonic Cell Identities during Lineage Priming.
Senft, A.D., Costello, I., King, H.W., Mould, A.W., Bikoff, E.K. and Robertson E.J.
Cell Reports – 24(8): 1977-1985.e7.
2017
Functional characterisation of cis-regulatory elements governing dynamic Eomes expression in the early mouse embryo.
Simon, C.S., Downes, D.J., Gosden, M.E., Telenius, J., Higgs, D.R., Hughes, J.R., Costello, I., Bikoff, E.K. and Robertson, E.J.
Development – 144(7): 1249-1260.
2015
Lhx1 functions together with Otx2, Foxa2, and Ldb1 to govern anterior mesendoderm, node, and midline development.
Costello, I., Nowotschin, S., Sun, X., Mould, A.W., Hadjantonakis, A.K., Bikoff, E.K. and Robertson, E.J.
Genes Dev. – 29(20): 2108-22.