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Elife. September 25, 2017; 6

Lineage commitment of embryonic cells involves MEK1-dependent clearance of pluripotency regulator Ventx2.

Scerbo P , Marchal L , Kodjabachian L .

During early embryogenesis, cells must exit pluripotency and commit to multiple lineages in all germ-layers. How this transition is operated in vivo is poorly understood. Here, we report that MEK1 and the Nanog-related transcription factor Ventx2 coordinate this transition. MEK1 was required to make Xenopus pluripotent cells competent to respond to all cell fate inducers tested. Importantly, MEK1 activity was necessary to clear the pluripotency protein Ventx2 at the onset of gastrulation. Thus, concomitant MEK1 and Ventx2 knockdown restored the competence of embryonic cells to differentiate. Strikingly, MEK1 appeared to control the asymmetric inheritance of Ventx2 protein following cell division. Consistently, when Ventx2 lacked a functional PEST-destruction motif, it was stabilized, displayed symmetric distribution during cell division and could efficiently maintain pluripotency gene expression over time. We suggest that asymmetric clearance of pluripotency regulators may represent an important mechanism to ensure the progressive assembly of primitive embryonic tissues.

PubMed ID: 28654420
PMC ID: PMC5487210
Article link: Elife.

Genes referenced: bmp4 gsc map2k1 mapk1 mixer myc nodal nog pou5f3.1 pou5f3.3 sf1 sox2 t tp53 tub ventx1.1 ventx2.2 xk81a1

Morpholinos referenced: map2k1 MO1 map2k1 MO2 ventx2.1 MO2

Boroviak, 2014, Pubmed[+]

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