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Regulation of germ layer formation by pluripotency factors during embryogenesis.

ABSTRACT: The classical pluripotency factors Oct4, Klf4, Sox2, and Nanog are required for the maintenance of pluripotency and self-renewal of embryonic stem (ES) cells and can reprogram terminally differentiated cells into a pluripotent state. Alteration in the levels of these factors in ES cells will cause differentiation into different lineages, suggesting that they are critical determinants of cell fates. These factors show dynamic expression patterns during embryogenesis, in particular in the pluripotent or multipotent cells of an early stage embryo, implying that they are involved in the cell fate decision during early embryonic development. Functions and the underlying molecular mechanisms have been extensively studied for these factors in ES cells under cultured conditions. However, this does not mean that the results also hold true for intact embryos. In the review, I have summarized and discussed the findings on the functions and the underlying mechanisms of the classical pluripotency factors during early embryogenesis, in particular during germ layer formation.

SUBMITTER: Cao Y

PROVIDER: S-EPMC3602094 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Regulation of germ layer formation by pluripotency factors during embryogenesis.

Cao Ying Y

Cell & bioscience 20130311 1

The classical pluripotency factors Oct4, Klf4, Sox2, and Nanog are required for the maintenance of pluripotency and self-renewal of embryonic stem (ES) cells and can reprogram terminally differentiated cells into a pluripotent state. Alteration in the levels of these factors in ES cells will cause differentiation into different lineages, suggesting that they are critical determinants of cell fates. These factors show dynamic expression patterns during embryogenesis, in particular in the pluripot ...[more]

PMID: 23497659

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Project description:BackgroundCell-cell communication is essential in tissue patterning. In early amphibian development, mesoderm is formed in the blastula-stage embryo through inductive interactions in which vegetal cells act on overlying equatorial cells. Members of the TGF-beta family such as activin B, Vg1, derrière and Xenopus nodal-related proteins (Xnrs) are candidate mesoderm inducing factors, with further activity to induce endoderm of the vegetal region. TGF-beta-like ligands, including BMP, are also responsible for patterning of germ layers. In addition, FGF signaling is essential for mesoderm formation whereas FGF signal inhibition has been implicated in endoderm induction. Clearly, several signaling pathways are coordinated to produce an appropriate developmental output; although intracellular crosstalk is known to integrate multiple pathways, relatively little is known about extracellular coordination.Methodology/principal findingsHere, we show that Xenopus Tsukushi (X-TSK), a member of the secreted small leucine rich repeat proteoglycan (SLRP) family, is expressed in ectoderm, endoderm, and the organizer during early development. We have previously reported that X-TSK binds to and inhibits BMP signaling in cooperation with chordin. We now demonstrate two novel interactions: X-TSK binds to and inhibits signaling by FGF8b, in addition to binding to and enhancement of Xnr2 signaling. This signal integration by X-TSK at the extracellular level has an important role in germ layer formation and patterning. Vegetally localized X-TSK potentiates endoderm formation through coordination of BMP, FGF and Xnr2 signaling. In contrast, X-TSK inhibition of FGF-MAPK signaling blocks ventrolateral mesoderm formation, while BMP inhibition enhances organizer formation. These actions of X-TSK are reliant upon its expression in endoderm and dorsal mesoderm, with relative exclusion from ventrolateral mesoderm, in a pattern shaped by FGF signals.Conclusions/significanceBased on our observations, we propose a novel mechanism by which X-TSK refines the field of positional information by integration of multiple pathways in the extracellular space.

Dataset Information

Regulation of germ layer formation by pluripotency factors during embryogenesis.

Publications

Regulation of germ layer formation by pluripotency factors during embryogenesis.

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