- MeSH
- Central Nervous System embryology MeSH
- Chick Embryo MeSH
- Regeneration MeSH
- Animals MeSH
- Check Tag
- Chick Embryo MeSH
- Animals MeSH
The apical-basal axis of the early plant embryo determines the body plan of the adult organism. To establish a polarized embryonic axis, plants evolved a unique mechanism that involves directional, cell-to-cell transport of the growth regulator auxin. Auxin transport relies on PIN auxin transporters, whose polar subcellular localization determines the flow directionality. PIN-mediated auxin transport mediates the spatial and temporal activity of the auxin response machinery that contributes to embryo patterning processes, including establishment of the apical (shoot) and basal (root) embryo poles. However, little is known of upstream mechanisms guiding the (re)polarization of auxin fluxes during embryogenesis. Here, we developed a model of plant embryogenesis that correctly generates emergent cell polarities and auxin-mediated sequential initiation of apical-basal axis of plant embryo. The model relies on two precisely localized auxin sources and a feedback between auxin and the polar, subcellular PIN transporter localization. Simulations reproduced PIN polarity and auxin distribution, as well as previously unknown polarization events during early embryogenesis. The spectrum of validated model predictions suggests that our model corresponds to a minimal mechanistic framework for initiation and orientation of the apical-basal axis to guide both embryonic and postembryonic plant development.
- MeSH
- Models, Biological * MeSH
- Biological Transport MeSH
- Indoleacetic Acids metabolism MeSH
- Cell Polarity MeSH
- Plant Growth Regulators metabolism MeSH
- Plant Proteins metabolism physiology MeSH
- Body Patterning MeSH
- Seeds growth & development MeSH
- Carrier Proteins metabolism physiology MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Establishment of the embryonic axis foreshadows the main body axis of adults both in plants and in animals, but underlying mechanisms are considered distinct. Plants utilize directional, cell-to-cell transport of the growth hormone auxin to generate an asymmetric auxin response that specifies the embryonic apical-basal axis. The auxin flow directionality depends on the polarized subcellular localization of PIN-FORMED (PIN) auxin transporters. It remains unknown which mechanisms and spatial cues guide cell polarization and axis orientation in early embryos. Herein, we provide conceptually novel insights into the formation of embryonic axis in Arabidopsis by identifying a crucial role of localized tryptophan-dependent auxin biosynthesis. Local auxin production at the base of young embryos and the accompanying PIN7-mediated auxin flow toward the proembryo are required for the apical auxin response maximum and the specification of apical embryonic structures. Later in embryogenesis, the precisely timed onset of localized apical auxin biosynthesis mediates PIN1 polarization, basal auxin response maximum, and specification of the root pole. Thus, the tight spatiotemporal control of distinct local auxin sources provides a necessary, non-cell-autonomous trigger for the coordinated cell polarization and subsequent apical-basal axis orientation during embryogenesis and, presumably, also for other polarization events during postembryonic plant life.
- MeSH
- Arabidopsis embryology MeSH
- Indoleacetic Acids metabolism pharmacology MeSH
- Membrane Transport Proteins metabolism MeSH
- Arabidopsis Proteins metabolism MeSH
- Plant Growth Regulators metabolism pharmacology physiology MeSH
- Body Patterning drug effects MeSH
- Seeds drug effects growth & development MeSH
- Protein Transport MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Studies of human embryonic stem cells (hESCs) commonly describe the nonfunctional p53-p21 axis of the G1/S checkpoint pathway with subsequent relevance for cell cycle regulation and the DNA damage response (DDR). Importantly, p21 mRNA is clearly present and upregulated after the DDR in hESCs, but p21 protein is not detectable. In this article, we provide evidence that expression of p21 protein is directly regulated by the microRNA (miRNA) pathway under standard culture conditions and after DNA damage. The DDR in hESCs leads to upregulation of tens of miRNAs, including hESC-specific miRNAs such as those of the miR-302 family, miR-371-372 family, or C19MC miRNA cluster. Most importantly, we show that the hESC-enriched miRNA family miR-302 (miR-302a, miR-302b, miR-302c, and miR-302d) directly contributes to regulation of p21 expression in hESCs and, thus, demonstrate a novel function for miR-302s in hESCS. The described mechanism elucidates the role of miRNAs in regulation of important molecular pathway governing the G1/S transition checkpoint before as well as after DNA damage.
- MeSH
- Cell Differentiation genetics physiology MeSH
- Cell Line MeSH
- Embryonic Stem Cells metabolism MeSH
- Cyclin-Dependent Kinase Inhibitor p21 genetics metabolism MeSH
- In Situ Nick-End Labeling MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Humans MeSH
- MicroRNAs genetics MeSH
- Tumor Suppressor Protein p53 genetics metabolism MeSH
- DNA Damage genetics MeSH
- Blotting, Western MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Among the 10 Frizzled (FZD) isoforms belonging to the Class F of G protein-coupled receptors (GPCRs), FZD10 remains the most enigmatic. FZD10 shows homology to FZD4 and FZD9 and was previously implicated in both β-catenin-dependent and -independent signalling. In normal tissue, FZD10 levels are generally very low; however, its upregulation in synovial carcinoma has attracted some attention for therapy. Our findings identify FZD10 as a receptor interacting with and signalling through the heterotrimeric G protein Gα13 but not Gα12, Gαi1, GαoA, Gαs, or Gαq. Stimulation with the FZD agonist WNT induced the dissociation of the Gα13 protein from FZD10, and led to global Gα12/13-dependent cell changes assessed by dynamic mass redistribution measurements. Furthermore, we show that FZD10 mediates Gα12/13 activation-dependent induction of YAP/TAZ transcriptional activity. In addition, we show a distinct expression of FZD10 in embryonic CNS endothelial cells at E11.5-E14.5. Given the well-known importance of Gα13 signalling for the development of the vascular system, the selective expression of FZD10 in brain vascular endothelial cells points at a potential role of FZD10-Gα13 signalling in CNS angiogenesis.
- MeSH
- Cell Line MeSH
- Central Nervous System blood supply MeSH
- Endothelium, Vascular drug effects metabolism MeSH
- Frizzled Receptors metabolism MeSH
- Neovascularization, Physiologic * MeSH
- Humans MeSH
- Mice, Inbred C57BL MeSH
- Dishevelled Proteins metabolism MeSH
- GTP-Binding Protein alpha Subunits, G12-G13 metabolism MeSH
- Wnt Proteins pharmacology MeSH
- Signal Transduction * MeSH
- Protein Binding drug effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
