RETRACTED: Cdx2 Gene Expression and Trophectoderm Lineage Specification in Mouse Embryos

Abstract

Controversy exists as to whether individual blastomeres from two-cell-stage mouse embryos have identical developmental properties and fate. We show that the transcription factor Cdx2 is expressed in the nuclei of cells derived from the late-dividing but not the first-dividing blastomere of two-cell embryos and, by lineage tracing and RNA interference knock-down experiments, that this lagging cell is the precursor of trophectoderm. Cdx2 mRNA is localized toward the vegetal pole of oocytes, reorients after fertilization, and becomes concentrated in the late-dividing, two-cell-stage blastomere. The asymmetrical distribution of Cdx2 gene products in the oocyte and embryo defines the lineage to trophectoderm.

Cell and molecular regulation of the mouse blastocyst

“…Recently, it has been suggested that localized maternal Cdx2 mRNA and protein can be detected before the eight-cell stage and that maternal Cdx2 is involved in TE formation (Deb et al, 2006). However, knockdown experiments using RNA interference strategies have led to conflicting results, with one group finding preblastocyst lethality (Deb et al, 2006) and another finding phenocopy of zygotic null Cdx2 mutants (Meissner and Jaenisch, 2006).…”

“…However, knockdown experiments using RNA interference strategies have led to conflicting results, with one group finding preblastocyst lethality (Deb et al, 2006) and another finding phenocopy of zygotic null Cdx2 mutants (Meissner and Jaenisch, 2006). Ultimate proof of the functional role of maternal Cdx2 will be provided by analysis of germline null mutants.…”

“…Recently, Deb et al (2006) reported localization of maternal Cdx2 mRNA to one half of the oocyte and to only one of the two-cell blastomeres (Deb et al, 2006). Using a combination of a time course of Cdx2 expression and lineage tracing, the Cdx2-expressing blastomere and its descendents were proposed to divide later than the nonexpressing blastomere and, surprisingly, to give rise to the entire tro-phectoderm (both mural and polar), occupying both embryonic and abembryonic regions of the blastocyst.…”

Mammalian nuclear transfer

“…In fact, the lack of the TE lineage generates a "biological artifact" (Hurlbut, 2005), because it creates a disorganized clump of cells. Detailed studies from the laboratories of Rossant and Beck provided excellent insight into the role of Cdx2 (Chawengsaksophak et al, 1997(Chawengsaksophak et al, , 2004Strumpf et al, 2005), the earliest known TE-specific transcription factor (Strumpf et al, 2005;Deb et al, 2006).…”

Mesenchymal Stem Cells: Possibilities of New Treatment Options

“…In mice, whether a blastomere is to become a trophoblast or an ICM cell appears to be specifi ed by its position during the fi rst cleavage (Piotrowska et al 2001 ) . It was also demonstrated that asymmetrical distribution of the Cdx2 gene product in mouse oocytes and embryos defi nes the lineage of the trophectoderm (Deb et al 2006 ) . In correlation with studies in which a signal for ICM or trophectoderm lineage is present in some blastomeres far earlier than when the phenotypical characteristics emerge, the earliest signs of cellular differentiation occur during the compaction stage in human embryos (Piotrowska et al 2001 ;Edwards 2005 ;Hansis et al 2004 ) .…”