FGF, insulin, and SMAD signaling cooperate for avian primordial germ cell self-renewal

Jemima Whyte, James D. Glover, Mark Woodcock, Joanna Brzeszczynska, Lorna Taylor, Adrian Sherman, Pete Kaiser, Michael J. McGrew

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1171-1182
Number of pages12
JournalStem Cell Reports
Volume5
Issue number6
DOIs
Publication statusE-pub ahead of print - 19 Nov 2015
Externally publishedYes

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