title: Primordial germ cell specification: a context-dependent cellular differentiation event [corrected].
abstract: During embryonic development, the foundation of the germline is laid by the specification of primordial germ cells (PGCs) from the postimplantation epiblast via bone morphogenetic protein (BMP) and WNT signalling. While the majority of epiblast cells undergo differentiation towards somatic cell lineages, PGCs initiate a unique cellular programme driven by the cooperation of the transcription factors BLIMP1, PRDM14 and AP2γ. These factors synergistically suppress the ongoing somatic differentiation and drive the re-expression of pluripotency and germ cell-specific genes accompanied by global epigenetic changes. However, an unresolved question is how postimplantation epiblast cells acquire the developmental competence for the PGC fate downstream of BMP/WNT signalling. One emerging concept is that transcriptional enhancers might play a central role in the establishment of developmental competence and the execution of cell fate determination. Here, we discuss recent advances on the specification and reprogramming of PGCs thereby highlighting the concept of enhancer function.
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK Department of Physiology, Development and Neuroscience, University of Cambridge, Downing St., Cambridge CB2 3DY, UK Wellcome Trust Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
authors.forename: Ufuk
authors.initials: U
authors.lastname: Günesdogan
authors.affiliation: Department of Biochemistry and Molecular Biology, BioMedical Center, University of Iceland, 101 Reykjavík, Iceland.
authors.forename: Erna
authors.initials: E
authors.lastname: Magnúsdóttir
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK Department of Physiology, Development and Neuroscience, University of Cambridge, Downing St., Cambridge CB2 3DY, UK Wellcome Trust Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK a.surani@gurdon.cam.ac.uk.
authors.forename: M Azim
authors.initials: MA
authors.lastname: Surani
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D047108:Embryonic Development / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000235:genetics*; D005855:Germ Layers / Q000196:embryology*; D051379:Mice; D008954:Models, Biological; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
keywords: developmental competence; enhancer; epigenetic reprogramming; primordial germ cells; specification