title: FGF, Insulin, and SMAD Signaling Cooperate for Avian Primordial Germ Cell Self-Renewal.
abstract: Precise self-renewal of the germ cell lineage is fundamental to fertility and reproductive success. The early precursors for the germ lineage, primordial germ cells (PGCs), survive and proliferate in several embryonic locations during their migration to the embryonic gonad. By elucidating the active signaling pathways in migratory PGCs in vivo, we were able to create culture conditions that recapitulate this embryonic germ cell environment. In defined medium conditions without feeder cells, the growth factors FGF2, insulin, and Activin A, signaling through their cognate-signaling pathways, were sufficient for self-renewal of germline-competent PGCs. Forced expression of constitutively active MEK1, AKT, and SMAD3 proteins could replace their respective upstream growth factors. Unexpectedly, we found that BMP4 could replace Activin A in non-clonal growth conditions. These defined medium conditions identify the key molecular pathways required for PGC self-renewal and will facilitate efforts in biobanking of chicken genetic resources and genome editing.
authors.affiliation: The Roslin Institute and Royal Dick School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK.
authors.forename: Jemima
authors.initials: J
authors.lastname: Whyte
authors.affiliation: The Roslin Institute and Royal Dick School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK.
authors.forename: James D
authors.initials: JD
authors.lastname: Glover
authors.affiliation: The Roslin Institute and Royal Dick School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodcock
authors.affiliation: The Roslin Institute and Royal Dick School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Brzeszczynska
authors.affiliation: The Roslin Institute and Royal Dick School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK.
authors.forename: Lorna
authors.initials: L
authors.lastname: Taylor
authors.affiliation: The Roslin Institute and Royal Dick School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Sherman
authors.affiliation: The Roslin Institute and Royal Dick School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK.
authors.forename: Pete
authors.initials: P
authors.lastname: Kaiser
authors.affiliation: The Roslin Institute and Royal Dick School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK. Electronic address: mike.mcgrew@roslin.ed.ac.uk.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McGrew
mesh_terms: D028341:Activins / Q000378:metabolism; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D002642:Chick Embryo / Q000166:cytology* / Q000378:metabolism; D002645:Chickens; D000066473:Embryonic Germ Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D007328:Insulin; D051785:Smad Proteins; D028341:Activins; D005346:Fibroblast Growth Factors