TGFß signaling pathways governing cell lineage commitment in the early mammalian embryo
TGFβ-signaling pathways play pre-eminent roles in the early post-implantation stage mouse embryo. Reciprocal inductive interactions between the epiblast and extra-embryonic lineages of the extra-embryonic ectoderm and visceral endoderm are required to pattern the epiblast, maintain cell identity and establish initial polarity. The precise balance of Nodal and BMP signaling orchestrates the proper establishment of the early axis, and cell type specification during gastrulation. Our recent experiments using mutant ES cells lacking Smad2/3 effectors downstream of Nodal signalling show this pathway is required to maintain embryonic and extra-embryonic cell identity during lineage priming prior to cell fate specification into mesoderm, endoderm and to balance Nodal/Bmp signalling during ectoderm differentiation. We have also been using a genetic approach to evaluate how the intersection of BMP and Nodal signals at the embryonic/extraembryonic interface are responsible for both specifying and maintaining the primordial germ cells of the embryo.
Liz received her BA in Zoology at Oxford (1978), and then pursued a PhD, followed by post-doctoral training with Martin Evans in the Department of Genetics at Cambridge. In 1988, she joined the faculty of the Department of Genetics and Development at Columbia University Medical School, New York where her lab was one of the first to report successful gene targeting experiments to reveal functional roles under physiological conditions in vivo. In 1992 Liz was recruited to Harvard University where over the next decade she studied the Nodal signalling pathway, discovering its critical role in both anterior-posterior and left-right axis patterning of the early mammalian embryo. Her lab also identified requirements for the zinc finger transcriptional repressor Blimp1 during specification of the mammalian germ line. She is currently a Wellcome Trust Principal Research Fellow and Professor of Developmental Biology in the Dunn School of Pathology, University of Oxford where her lab has focused on transcriptional networks governing cell fate decisions in the embryo and controlling adult tissue homeostasis. Liz is a Fellow of the Royal Society and the Academy of Medical Sciences, a member of EMBO and a former Chair of the British Society for Developmental Biology.