title: Developmental differences in the expression of FGF receptors between human and mouse embryos.
abstract: BACKGROUND
  Fibroblast growth factor (FGF) signaling is essential for early trophoblast expansion and maintenance in the mouse, but is not required for trophectoderm specification during blastocyst formation. This signaling pathway is stably activated to expand the trophoblast stem cell compartment in vivo, while in vitro, FGFs are used for the derivation of trophoblast stem (TS) cells from blastocysts and early post-implantation mouse embryos. However, the function of FGFs during human trophoblast development is not known.
  
  
  METHODS
  We sought to derive TS cells from human blastocysts in a number of culture conditions, including in the presence of FGFs and stem cell factor (SCF). We also investigated the expression of FGF receptors (FGFRs) in blastocysts, and the expression of FGFR2 and activated ERK1/2 in first trimester human placentae.
  
  
  RESULTS
  We found that SCF, but not FGF2/4, improved the quality of blastocyst outgrowths, but we were unable to establish stable human TS cell lines. We observed CDX2 expression in the trophectoderm of fully blastocysts, but rarely observed transcription of FGFRs. FGFR2 protein was not detected in human blastocysts, but was strongly expressed in mouse blastocysts. However, we found robust FGFR2 expression and activated ERK1/2 in the cytotrophoblast layer of early human placenta.
  
  
  CONCLUSIONS
  Our data suggests that initiation of FGF-dependent trophoblast expansion may occur later in human development, and is unlikely to drive maintenance of a TS cell compartment during the peri-implantation period. These findings suggest that cytotrophoblast preparations from early placentae may be a potential source of FGF-dependent human TS cells.
authors.affiliation: MRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK. Electronic address: tilo.kunath@ed.ac.uk.
authors.forename: T
authors.initials: T
authors.lastname: Kunath
authors.affiliation: Rosalind and Morris Goodman Cancer Research Centre, Department of Human Genetics, McGill University, 1160 Pine Avenue West, Montréal, Quebec H3A 1A3, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamanaka
authors.affiliation: Department of Obstetrics and Gynecology, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, Ontario M5T 3H7, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Detmar
authors.affiliation: Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4, Canada.
authors.forename: D
authors.initials: D
authors.lastname: MacPhee
authors.affiliation: Department of Obstetrics and Gynecology, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, Ontario M5T 3H7, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Caniggia
authors.affiliation: Department of Obstetrics and Gynecology, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, Ontario M5T 3H7, Canada; Program in Developmental & Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Rossant
authors.affiliation: Department of Obstetrics and Gynecology, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, Ontario M5T 3H7, Canada. Electronic address: jurisicova@lunenfeld.ca.
authors.forename: A
authors.initials: A
authors.lastname: Jurisicova
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D011247:Pregnancy; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
chemical_list: D017468:Receptors, Fibroblast Growth Factor
keywords: Blastocyst; CDX2; FGF receptors; FGFR2; Human; Mouse; Trophoblast