A POU protein regulates mesodermal competence to FGF in Xenopus

Henig, Clara; Elias, Sarah; Frank, Dale

doi:10.1016/s0925-4773(98)00006-9

Cited by 21 publications

(33 citation statements)

References 65 publications

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“…These results identify Oct3/4 as a factor contributing to the expression of the Cdx genes and actually activating one of the factors involved in its own repression. Several studies have shown that during gastrulation, the Xenopus Oct3/4 factors function in a manner consistent with the active maintenance of the pluripotent state like their mammalian homologues (Henig et al, 1998;Cao et al, 2006Cao et al, , 2007Morrison and Brickman, 2006;Snir et al, 2006). Thus, Cdx1 acting as a negative regulator of the Pou5f1 genes during gastrulation, would ultimately function to end the undifferentiated state and facilitate the transition into gastrulation.…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies support the functional conservation between mouse Oct3/4 and the Xenopus Pou5f1 genes. The Xenopus Pou5f1 genes perform functions consistent with the maintenance of pluripotency, the regulation of gastrulation, the prevention of germ layer differentiation, and they can even maintain the pluripotency of mouse ES cells to different extents (Henig et al, 1998;Cao et al, 2006Cao et al, , 2007Morrison and Brickman, 2006;Snir et al, 2006). Also, the murine Oct3/4 protein can rescue the developmental malformations resulting from knock-down of the frog Pou5f1 gene activities (Cao et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Negative autoregulation of Oct3/4 through Cdx1 promotes the onset of gastrulation

et al. 2011

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Gastrulation marks the onset of germ layer formation from undifferentiated precursor cells maintained by a network including the Pou5f1 gene, Oct3/4. Negative regulation of the undifferentiated state is a prerequisite for germ layer formation and subsequent development. A novel cross-regulatory network was characterized including the Pou5f1 and Cdx1 genes as part of the signals controlling the onset of gastrulation. Of particular interest was the observation that, preceding gastrulation, the Xenopus Oct3/4 factors, Oct60, Oct25, and Oct91, positively regulate Cdx1 expression through FGF signaling, and during gastrulation the Oct3/4 factors become repressors of Cdx1. Cdx1 negatively regulates the Pou5f1 genes during gastrulation, thus contributing to the repression of the network maintaining the undifferentiated state and promoting the onset of gastrulation. These regulatory interactions suggest that Oct3/4 initiates its own negative autoregulation through Cdx1 up-regulation to begin the repression of pluripotency in preparation for the onset of gastrulation and germ layer differentiation. Developmental Dynamics 240:796-807,

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Negative autoregulation of Oct3/4 through Cdx1 promotes the onset of gastrulation

et al. 2011

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“…5C). GATA4 was detected, but not GATA5/6, Xhex, Chordin or Cerberus, which are all expressed in more anterior mesendoderm and involved in anterior patterning (Bouwmeester et al, 1996;Gove et al, 1997;Henig et al, 1998;Henry and Melton, 1998;Kelley et al, 1993;Smithers and Jones, 2002;Tao et al, 2005;Weber et al, 2000;Xanthos et al, 2001). Xwnt11, an anterior dorsalizing factor that lies upstream of Xhex activity, was not expressed in Nanos1-depleted PGCs.…”

Section: Fig 4 Nanos1-depleted Pgcs Exhibit Ctd-pser2 Prematurelymentioning

confidence: 99%

“…5C). Oct91, a homolog of Oct3/4 (Pou5f1) in mammals, functions as a pluripotent factor to preserve the uncommitted states of early blastomeres (Cao et al, 2007;Henig et al, 1998) and the germline (F.L. and M.L.K., unpublished) (Venkatarama et al, 2010).…”

Section: Expression Of Endoderm Genes In Nanos1 Morphantsmentioning

confidence: 99%

XenopusNanos1 is required to prevent endoderm gene expression and apoptosis in primordial germ cells

2012

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Nanos is expressed in multipotent cells, stem cells and primordial germ cells (PGCs) of organisms as diverse as jellyfish and humans. It functions together with Pumilio to translationally repress targeted mRNAs. Here we show by loss-of-function experiments that Xenopus Nanos1 is required to preserve PGC fate. Morpholino knockdown of maternal Nanos1 resulted in a striking decrease in PGCs and a loss of germ cells from the gonads. Lineage tracing and TUNEL staining reveal that Nanos1-deficient PGCs fail to migrate out of the endoderm. They appear to undergo apoptosis rather than convert to normal endoderm. Whereas normal PGCs do not become transcriptionally active until neurula, Nanos1-depleted PGCs prematurely exhibit a hyperphosphorylated RNA polymerase II C-terminal domain at the midblastula transition. Furthermore, they inappropriately express somatic genes characteristic of endoderm regulated by maternal VegT, including Xsox17α, Bix4, Mixer, GATA4 and Edd. We further demonstrate that Pumilio specifically binds VegT RNA in vitro and represses, along with Nanos1, VegT translation within PGCs. Repressed VegT RNA in wild-type PGCs is significantly less stable than VegT in Nanos1-depleted PGCs. Our data indicate that maternal VegT RNA is an authentic target of Nanos1/Pumilio translational repression. We propose that Nanos1 functions to translationally repress RNAs that normally specify endoderm and promote apoptosis, thus preserving the germline.

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“…Like their mouse counterparts, they control pluripotency maintenance in embryos, suppressing BMP-mediated ventral fate acquisition, inhibiting Activin-and FGF-induced mesodermal commitment, and promoting neural tissue formation. This activity contributes to maintaining proper tissue boundaries and preventing expansion of mesodermal and endodermal territories into pluripotent ectoderm (Cao et al, 2006;Henig et al, 1998;Morrison and Brickman, 2006;Snir et al, 2006;Takebayashi-Suzuki et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Geminin cooperates with Polycomb to restrain multi-lineage commitment in the early embryo

et al. 2011

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SUMMARYTransient maintenance of a pluripotent embryonic cell population followed by the onset of multi-lineage commitment is a fundamental aspect of development. However, molecular regulation of this transition is not well characterized in vivo. Here, we demonstrate that the nuclear protein Geminin is required to restrain commitment and spatially restrict mesoderm, endoderm and non-neural ectoderm to their proper locations in the Xenopus embryo. We used microarray analyses to demonstrate that Geminin overexpression represses many genes associated with cell commitment and differentiation, while elevating expression levels of genes that maintain pluripotent early and immature neurectodermal cell states. We characterized the relationship of Geminin to cell signaling and found that Geminin broadly represses Activin-, FGF-and BMP-mediated cell commitment. Conversely, Geminin knockdown enhances commitment responses to growth factor signaling and causes ectopic mesodermal, endodermal and epidermal fate commitment in the embryo. We also characterized the functional relationship of Geminin with transcription factors that had similar activities and found that Geminin represses commitment independent of Oct4 ortholog (Oct25/60) activities, but depends upon intact Polycomb repressor function. Consistent with this, chromatin immunoprecipitation assays directed at mesodermal genes demonstrate that Geminin promotes Polycomb binding and Polycomb-mediated repressive histone modifications, while inhibiting modifications associated with gene activation. This work defines Geminin as an essential regulator of the embryonic transition from pluripotency through early multi-lineage commitment, and demonstrates that functional cooperativity between Geminin and Polycomb contributes to this process.

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A POU protein regulates mesodermal competence to FGF in Xenopus

Cited by 21 publications

References 65 publications

Negative autoregulation of Oct3/4 through Cdx1 promotes the onset of gastrulation

Negative autoregulation of Oct3/4 through Cdx1 promotes the onset of gastrulation

XenopusNanos1 is required to prevent endoderm gene expression and apoptosis in primordial germ cells

Geminin cooperates with Polycomb to restrain multi-lineage commitment in the early embryo

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