Regulation of chromatin accessibility by Tbx factors guiding embryonic cell lineage specification


Project Summary

Cell identities are established during embryonic development and maintained throughout life. We demonstrated that the first specification event that segregates neuroectoderm from mesoderm and endoderm lineages is regulated by the Tbx transcription factors Eomes and Brachyury. We will analyse the dynamic changes in chromatin state during early exit from pluripotency and characterise the role of Eomes and Brachyury for recruitment of chromatin remodelling activities. This project aims at understanding the establishment of discrete cell lineage identities during the first lineage decision of early mammalian development.

Selected project-relevant publications

  • Schüle K.M., Weckerle J., Probst S., Wehmeyer A.E., Zissel L., Schröder C.M., Tekman M., Kim G.J., Schlägl I.M., Sagar and Arnold S.J. (2023) Eomes restricts Brachyury functions at the onset of mouse gastrulation. Dev Cell 58, 1627-1642.e1627.
  • Wehmeyer A.E., Schüle K.M., Conrad A., Schröder C.M., Probst S. and Arnold S.J. (2022) Chimeric 3D gastruloids – a versatile tool for studies of mammalian peri-gastrulation development. Development 149, doi 10.1242/dev.200812.
  • Probst S., Sagar, Tosic J., Schwan C., Grün D. and Arnold S.J. (2021) Spatiotemporal sequence of mesoderm and endoderm lineage segregation during mouse gastrulation. Development 148, doi 10.1242/dev.193789.
  • Fixemer J., Hummel J.F., Arnold F., Klose C.S.N., Hofherr A., Weissert K., Kögl T., Köttgen M., Arnold S.J., Aichele P. and Tanriver Y. (2020) Eomes cannot replace its paralog T-bet during expansion and differentiation of CD8 effector T cells. PLoS Pathog 16, e1008870.
  • Tosic J., Kim G.J., Pavlovic M., Schröder C.M., Mersiowsky S.L., Barg M., Hofherr A., Probst S., Köttgen M., Hein L. and Arnold S.J. (2019) Eomes and Brachyury control pluripotency exit and germ-layer segregation by changing the chromatin state. Nat Cell Biol 21, 1518-1531.
  • Kaminski M.M., Tosic J., Kresbach C., Engel H., Klockenbusch J., Muller A.L., Pichler R., Grahammer F., Kretz O., Huber T.B., Walz G., Arnold S.J. and Lienkamp S.S. (2016) Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors. Nat Cell Biol 18, 1269-1280.
  • Funk M.C., Bera A.N., Menchen T., Kuales G., Thriene K., Lienkamp S.S., Dengjel J., Omran H., Frank M. and Arnold S.J. (2015) Cyclin O (Ccno) functions during deuterosome-mediated centriole amplification of multiciliated cells. EMBO J 34, 1078-1089.
  • Zhu D., Holz S., Metzger E., Pavlovic M., Jandausch A., Jilg C., Galgoczy P., Herz C., Moser M., Metzger D., Gunther T., Arnold S.J. and Schule R. (2014) Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells. Nat Commun 5, 3174.
  • Klose C.S.N., Flach M., Mohle L., Rogell L., Hoyler T., Ebert K., Fabiunke C., Pfeifer D., Sexl V., Fonseca-Pereira D., Domingues R.G., Veiga-Fernandes H., Arnold S.J., Busslinger M., Dunay I.R., Tanriver Y. and Diefenbach A. (2014) Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. Cell 157, 340-356.
  • Teo A.K., Arnold S.J., Trotter M.W., Brown S., Ang L.T., Chng Z., Robertson E.J., Dunn N.R. and Vallier L. (2011) Pluripotency factors regulate definitive endoderm specification through eomesodermin. Genes Dev 25, 238-250.
  • Costello I., Pimeisl I.M., Drager S., Bikoff E.K., Robertson E.J. and Arnold S.J. (2011) The T-box transcription factor Eomesodermin acts upstream of Mesp1 to specify cardiac mesoderm during mouse gastrulation. Nat Cell Biol 13, 1084-1091.
  • Arnold S.J. and Robertson E.J. (2009) Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo. Nat Rev Mol Cell Biol 10, 91-103.
  • Arnold S.J., Huang G.J., Cheung A.F., Era T., Nishikawa S., Bikoff E.K., Molnar Z., Robertson E.J. and Groszer M. (2008) The T-box transcription factor Eomes/Tbr2 regulates neurogenesis in the cortical subventricular zone. Genes Dev 22, 2479-2484.
  • Arnold S.J., Hofmann U.K., Bikoff E.K. and Robertson E.J. (2008) Pivotal roles for eomesodermin during axis formation, epithelium-to-mesenchyme transition and endoderm specification in the mouse. Development 135, 501-511.