title: Stochastic specification of primordial germ cells from mesoderm precursors in axolotl embryos.
abstract: A common feature of development in most vertebrate models is the early segregation of the germ line from the soma. For example, in Xenopus and zebrafish embryos primordial germ cells (PGCs) are specified by germ plasm that is inherited from the egg; in mice, Blimp1 expression in the epiblast mediates the commitment of cells to the germ line. How these disparate mechanisms of PGC specification evolved is unknown. Here, in order to identify the ancestral mechanism of PGC specification in vertebrates, we studied PGC specification in embryos from the axolotl (Mexican salamander), a model for the tetrapod ancestor. In the axolotl, PGCs develop within mesoderm, and classic studies have reported their induction from primitive ectoderm (animal cap). We used an axolotl animal cap system to demonstrate that signalling through FGF and BMP4 induces PGCs. The role of FGF was then confirmed in vivo. We also showed PGC induction by Brachyury, in the presence of BMP4. These conditions induced pluripotent mesodermal precursors that give rise to a variety of somatic cell types, in addition to PGCs. Irreversible restriction of the germ line did not occur until the mid-tailbud stage, days after the somatic germ layers are established. Before this, germline potential was maintained by MAP kinase signalling. We propose that this stochastic mechanism of PGC specification, from mesodermal precursors, is conserved in vertebrates.
authors.affiliation: School of Life Sciences, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Jodie
authors.initials: J
authors.lastname: Chatfield
authors.affiliation: School of Life Sciences, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: O'Reilly
authors.affiliation: Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Rosemary F
authors.initials: RF
authors.lastname: Bachvarova
authors.affiliation: School of Life Sciences, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ferjentsik
authors.affiliation: School of Life Sciences, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Redwood
authors.affiliation: Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford OX3 9DS, UK.
authors.forename: Maggie
authors.initials: M
authors.lastname: Walmsley
authors.affiliation: Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford OX3 9DS, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Patient
authors.affiliation: School of Life Sciences, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Mathew
authors.initials: M
authors.lastname: Loose
authors.affiliation: School of Life Sciences, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, UK andrew.d.johnson@nottingham.ac.uk.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Johnson
mesh_terms: D000558:Ambystoma mexicanum / Q000196:embryology*; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002454:Cell Differentiation; D005326:Fetal Proteins / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology*; D017403:In Situ Hybridization; D020935:MAP Kinase Signaling System; D008648:Mesoderm / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology; D015398:Signal Transduction; D013269:Stochastic Processes; D020825:T-Box Domain Proteins / Q000378:metabolism; D014981:Xenopus; D000098908:Brachyury Protein
chemical_list: D055415:Bone Morphogenetic Protein 4; D005326:Fetal Proteins; D005346:Fibroblast Growth Factors; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein
keywords: Axolotl; Evolution; Germ plasm; Mesoderm; PGC; Pluripotency; Primordial germ cell