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

Abstract

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.DOI: http://dx.doi.org/10.7554/eLife.21526.001

The vertebrate-specific VENTX/NANOG gene empowers neural crest with ectomesenchyme potential

“…Ventx2-depleted embryos developed medullary and extramedullary sensory neurons, the vertebrate homologs of invertebrate proto-NC cells (e.g., the urochordate BTNs) (18,21,22). In addition, we showed that sustained Ventx2 activity during late gastrulation, but not before, enhanced NC identity, suggesting that the developmental function of Ventx2 in promoting NC identity was uncoupled from its role in pluripotent blastula cells (24)(25)(26)(27)(28)(29)(30)(31)(32)(33). Activation of Ventx2 during late gastrulation led to the local expansion of the stem cell marker (pou5f3.1/ oct4) and increased expression of other genes linked to broad developmental potential and reprogramming (tert, tet3, kdm4a, smarcA4, and chd7).…”

“…To date, the architecture of the NB/NC circuitry is a constrained and synapomorphic trait of bilaterians, whereas expression of ventx, nanog, and ved in NB/NC cells is a synapomorphic trait of vertebrates (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30).…”

“…Controls included injected embryos grown in 0.2% ethanol and uninjected embryos grown in dexamethasone. The Ventx2-MO was described in (24,30). Embryos were injected unilaterally (in one dorsal-animal blastomere at the eight-cell stage) for whole-mount in situ hybridization (WISH)/morphology analyses.…”

Notch1 is asymmetrically distributed from the beginning of embryogenesis and controls the ventral center

“…In addition, Notch1 Mo downregulated other genes important for the ventral program, such as trim29 (Hayes et al, 2007;Cibois et al, 2015;Popov et al, 2017) (Fig. S6H), xk81a1 (Yan et al, 2009;Scerbo et al, 2017) (Fig. S6I) and tfap2a (Luo et al, 2002) (Fig.…”

Ventx Family and Its Functional Similarities with Nanog: Involvement in Embryonic Development and Cancer Progression

“…The suppressed expression of organizer-specific genes resulted in a headless phenotype. Studies have shown that Ventx2.2/Xom acts as a Nanog-like pluripotency marker in Xenopus [ 48 , 49 ]. Overexpressed Ventx2.2 stabilizes the cells’ pluripotency and inhibits multiple-cell-lineage commitment during the embryonic development of X. laevis .…”