Document Detail


Bone morphogenetic proteins regulate hinge point formation during neural tube closure by dynamic modulation of apicobasal polarity.
MedLine Citation:
PMID:  22865775     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Dae Seok Eom; Smita Amarnath; Jennifer L Fogel; Seema Agarwala
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-03
Journal Detail:
Title:  Birth defects research. Part A, Clinical and molecular teratology     Volume:  94     ISSN:  1542-0760     ISO Abbreviation:  Birth Defects Res. Part A Clin. Mol. Teratol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-16     Completed Date:  2013-03-14     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  101155107     Medline TA:  Birth Defects Res A Clin Mol Teratol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  804-16     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Affiliation:
Institute for Cell and Molecular Biology, University of Texas, Austin, TX 78712, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified
Body Patterning / genetics*
Bone Morphogenetic Proteins / genetics,  metabolism,  physiology*
Cell Movement / genetics,  physiology
Cell Polarity / genetics,  physiology
Chick Embryo
Kinetics
Morphogenesis / genetics,  physiology
Neural Crest / embryology*,  metabolism
Neural Plate / cytology,  embryology,  metabolism
Neural Tube / embryology*,  metabolism
Neural Tube Defects / embryology,  genetics
Neurulation / genetics*,  physiology
Signal Transduction / genetics,  physiology
Grant Support
ID/Acronym/Agency:
R01 NS049091/NS/NINDS NIH HHS; R01 NS049091/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Bone Morphogenetic Proteins
Comments/Corrections

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