Cell-cycle-dependent TGFβ-BMP antagonism regulates neural tube closure by modulating tight junctions
| Autor: | Smita Amarnath, Seema Agarwala |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Neural Tube Organogenesis Smad Proteins Chick Embryo Biology Bone morphogenetic protein Ligands Models Biological Tight Junctions 03 medical and health sciences Transforming Growth Factor beta Cell polarity medicine Animals Cell Lineage Phosphorylation Cell Shape Cell Nucleus Neural fold Tight junction Cell Cycle Neural tube Cell Polarity Cell Biology Cell biology Protein Transport 030104 developmental biology medicine.anatomical_structure Bone Morphogenetic Proteins Signal transduction Neural plate Signal Transduction Subcellular Fractions Research Article |
| Zdroj: | Journal of cell science. 130(1) |
| ISSN: | 1477-9137 |
| Popis: | Many organs form by invaginating and rolling flat epithelial cell sheets into tubes. Invagination of the ventral midline of the neural plate forms the median hinge point (MHP), an event that elevates the neural folds and is essential for neural tube closure (NTC). MHP formation involves dynamic spatiotemporal modulations of cell shape, but how these are achieved is not understood. Here, we show that cell-cycle-dependent BMP and TGFβ antagonism elicits MHP formation by dynamically regulating interactions between apical (PAR complex) and basolateral (LGL) polarity proteins. TGFβ and BMP-activated receptor (r)-SMADs [phosphorylated SMAD2 or SMAD3 (pSMAD2,3), or phosphorylated SMAD1, SMAD5 or SMAD8 (pSMAD1,5,8)] undergo cell-cycle-dependent modulations and nucleo-cytosolic shuttling along the apicobasal axis of the neural plate. Non-canonical TGFβ and BMP activity in the cytosol determines whether pSMAD2,3 or pSMAD1,5,8 associates with the tight junction (PAR complex) or with LGL, and whether cell shape changes can occur at the MHP. Thus, the interactions of BMP and TGFβ with polarity proteins dynamically modulate MHP formation by regulating r-SMAD competition for tight junctions and r-SMAD sequestration by LGL. |
| Databáze: | OpenAIRE |
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