title: Elf5 counteracts precocious trophoblast differentiation by maintaining Sox2 and 3 and inhibiting Hand1 expression.
abstract: In mice the transcription factor Elf5 is necessary for correct trophoblast development. Upon knockdown of Elf5, TS cells display neither a decrease in proliferation nor an increase in cell death but rather an increased propensity to differentiate. Such cells rapidly lose Sox2 and 3 expression, while transiently upregulating the giant cell differentiation determinant gene Hand1. Other genes affected within 24h of Elf5 knock-down, many of which have not previously been implicated in trophoblast development, exhibited in vivo expression domains and in vitro expression responses consistent with Elf5 having a role in counteracting trophoblast differentiation. In an ES to TS differentiation assay using Cdx2 overexpression with Elf5 loss of function cell lines, it was shown that Elf5 is necessary to prevent terminal trophoblast differentiation. This data thus suggest that Elf5 is a gatekeeper for the TS to differentiated trophoblast transition thereby preventing the precocious differentiation of the undifferentiated extraembryonic ectoderm.
authors.affiliation: AgResearch Ruakura, 10 Bisley Road, Hamilton 3214, New Zealand. Electronic address: dpearton@gmail.com.
authors.forename: David J
authors.initials: DJ
authors.lastname: Pearton
authors.affiliation: AgResearch Ruakura, 10 Bisley Road, Hamilton 3214, New Zealand. Electronic address: craig.smith@nd.edu.au.
authors.forename: Craig S
authors.initials: CS
authors.lastname: Smith
authors.affiliation: AgResearch Ruakura, 10 Bisley Road, Hamilton 3214, New Zealand. Electronic address: redgate.emma@gmail.com.
authors.forename: Emma
authors.initials: E
authors.lastname: Redgate
authors.affiliation: AgResearch Ruakura, 10 Bisley Road, Hamilton 3214, New Zealand; Department of Biological Sciences, University of Waikato, Hamilton 3214, New Zealand.
authors.forename: Jessica
authors.initials: J
authors.lastname: van Leeuwen
authors.affiliation: AgResearch Ruakura, 10 Bisley Road, Hamilton 3214, New Zealand.
authors.forename: Martyn
authors.initials: M
authors.lastname: Donnison
authors.affiliation: AgResearch Ruakura, 10 Bisley Road, Hamilton 3214, New Zealand; School of Biological Sciences, Victoria University of Wellington, PO Box 600, Wellington 6140, New Zealand. Electronic address: drplpepper@gmail.com.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Pfeffer
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D055785:Gene Knockdown Techniques; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014327:Trophoblasts / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; C500759:Elf5 protein, mouse; C095572:Hand1 protein, mouse; C527783:Sox2 protein, mouse; C527786:Sox3 protein, mouse
keywords: Elf5; Hand1; Secretin; Sox2; Sox3; Trophoblast