Bone morphogenetic proteins regulate hinge point formation during neural tube closure by dynamic modulation of apicobasal polarity
| Autor: | Smita Amarnath, Dae Seok Eom, Jennifer L. Fogel, Seema Agarwala |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Embryology
Interkinetic nuclear migration Neural Tube Chick Embryo Biology Bone morphogenetic protein Article Animals Genetically Modified Cell Movement Cell polarity medicine Morphogenesis Animals Neural Tube Defects Neurulation Body Patterning Neural fold Neural Plate Neural tube Cell Polarity Apical constriction General Medicine Anatomy Cell biology Kinetics medicine.anatomical_structure Neural Crest Pediatrics Perinatology and Child Health Bone Morphogenetic Proteins Neural plate Developmental Biology Signal Transduction |
| Zdroj: | Birth defects research. Part A, Clinical and molecular teratology. 94(10) |
| ISSN: | 1542-0760 |
| Popis: | BACKGROUND A critical event in neural tube closure is the formation of median hinge points (MHPs) and dorsolateral hinge points (DLHPs). Together, they buckle the ventral midline and elevate and juxtapose the neural folds for proper neural tube closure. Dynamic cell behaviors occur at hinge points (HPs), but their molecular regulation is largely unexplored. Bone morphogenetic proteins (BMPs) have been implicated in a variety of neural tube closure defects, although the underlying mechanisms are poorly understood. METHODS In this study, we used in vivo electroporations, high-resolution microscopy, and biochemical analyses to explore the role of BMP signaling in chick midbrain neural tube closure. RESULTS We identified a cell-cycle–dependent BMP gradient in the midbrain neural plate, which results in low-level BMP activity at the MHP. We show that although BMP signaling does not have a role in midbrain cell-fate specification, its attenuation is necessary and sufficient for MHP formation and midbrain closure. BMP blockade induces MHP formation by regulating apical constriction and basal nuclear migration. Furthermore, BMP signaling is critically important for maintaining epithelial organization by biochemically interacting with apicobasal polarity proteins (e.g., PAR3). As a result, prolonged BMP blockade disrupts apical junctions, desegregating the apical (PAR3+, ZO1+) and basolateral (LGL+) compartments. Direct apical LGL-GFP misexpression in turn is sufficient to induce ectopic HPs. CONCLUSIONS BMPs have a critical role in maintaining epithelial organization, a role that is conserved across species and tissue types. Its cell-cycle–dependent modulation in the neural plate dynamically regulates apicobasal polarity and helps to bend, shape, and close the neural tube. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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