PMID- 28607062
OWN - NLM
STAT- MEDLINE
DCOM- 20180509
LR  - 20181113
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 114
IP  - 26
DP  - 2017 Jun 27
TI  - Biomechanical coupling facilitates spinal neural tube closure in mouse embryos.
PG  - E5177-E5186
LID - 10.1073/pnas.1700934114 [doi]
AB  - Neural tube (NT) formation in the spinal region of the mammalian embryo involves 
      a wave of "zippering" that passes down the elongating spinal axis, uniting the
      neural fold tips in the dorsal midline. Failure of this closure process leads to 
      open spina bifida, a common cause of severe neurologic disability in humans.
      Here, we combined a tissue-level strain-mapping workflow with laser ablation of
      live-imaged mouse embryos to investigate the biomechanics of mammalian spinal
      closure. Ablation of the zippering point at the embryonic dorsal midline causes
      far-reaching, rapid separation of the elevating neural folds. Strain analysis
      revealed tissue expansion around the zippering point after ablation, but
      predominant tissue constriction in the caudal and ventral neural plate zone. This
      zone is biomechanically coupled to the zippering point by a supracellular F-actin
      network, which includes an actin cable running along the neural fold tips.
      Pharmacologic inhibition of F-actin or laser ablation of the cable causes neural 
      fold separation. At the most advanced somite stages, when completion of spinal
      closure is imminent, the cable forms a continuous ring around the neuropore, and 
      simultaneously, a new caudal-to-rostral zippering point arises. Laser ablation of
      this new closure initiation point causes neural fold separation, demonstrating
      its biomechanical activity. Failure of spinal closure in pre-spina bifida
      Zic2(Ku) mutant embryos is associated with altered tissue biomechanics, as
      indicated by greater neuropore widening after ablation. Thus, this study
      identifies biomechanical coupling of the entire region of active spinal
      neurulation in the mouse embryo as a prerequisite for successful NT closure.
FAU - Galea, Gabriel L
AU  - Galea GL
AUID- ORCID: 0000-0003-2515-1342
AD  - Newlife Birth Defects Research Centre, UCL Great Ormond Street Institute of Child
      Health, University College London, London WC1N 1EH, United Kingdom;
      g.galea@ucl.ac.uk.
FAU - Cho, Young-June
AU  - Cho YJ
AD  - Newlife Birth Defects Research Centre, UCL Great Ormond Street Institute of Child
      Health, University College London, London WC1N 1EH, United Kingdom.
FAU - Galea, Gauden
AU  - Galea G
AD  - Division of Noncommunicable Diseases and Promoting Health Through the Life
      Course, World Health Organization Regional Office for Europe, Copenhagen DK-2100,
      Denmark.
FAU - Mole, Matteo A
AU  - Mole MA
AD  - Newlife Birth Defects Research Centre, UCL Great Ormond Street Institute of Child
      Health, University College London, London WC1N 1EH, United Kingdom.
FAU - Rolo, Ana
AU  - Rolo A
AUID- ORCID: 0000-0002-8683-4991
AD  - Newlife Birth Defects Research Centre, UCL Great Ormond Street Institute of Child
      Health, University College London, London WC1N 1EH, United Kingdom.
FAU - Savery, Dawn
AU  - Savery D
AD  - Newlife Birth Defects Research Centre, UCL Great Ormond Street Institute of Child
      Health, University College London, London WC1N 1EH, United Kingdom.
FAU - Moulding, Dale
AU  - Moulding D
AD  - Newlife Birth Defects Research Centre, UCL Great Ormond Street Institute of Child
      Health, University College London, London WC1N 1EH, United Kingdom.
FAU - Culshaw, Lucy H
AU  - Culshaw LH
AD  - Newlife Birth Defects Research Centre, UCL Great Ormond Street Institute of Child
      Health, University College London, London WC1N 1EH, United Kingdom.
FAU - Nikolopoulou, Evanthia
AU  - Nikolopoulou E
AD  - Newlife Birth Defects Research Centre, UCL Great Ormond Street Institute of Child
      Health, University College London, London WC1N 1EH, United Kingdom.
FAU - Greene, Nicholas D E
AU  - Greene NDE
AUID- ORCID: 0000-0002-4170-5248
AD  - Newlife Birth Defects Research Centre, UCL Great Ormond Street Institute of Child
      Health, University College London, London WC1N 1EH, United Kingdom.
FAU - Copp, Andrew J
AU  - Copp AJ
AUID- ORCID: 0000-0002-2544-9117
AD  - Newlife Birth Defects Research Centre, UCL Great Ormond Street Institute of Child
      Health, University College London, London WC1N 1EH, United Kingdom.
LA  - eng
GR  - G0801124/Medical Research Council/United Kingdom
GR  - J003794/Medical Research Council/United Kingdom
GR  - 107474/Z/15/Z/Wellcome Trust/United Kingdom
GR  - 087525/Wellcome Trust/United Kingdom
GR  - Wellcome Trust/United Kingdom
GR  - 001/World Health Organization/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170612
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Actins)
RN  - 0 (Transcription Factors)
RN  - 0 (Zic2 protein, mouse)
SB  - IM
MH  - Actins
MH  - Animals
MH  - Embryo, Mammalian/cytology/*metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Mutant Strains
MH  - *Models, Biological
MH  - Neural Tube/cytology/*embryology
MH  - Transcription Factors/genetics/metabolism
PMC - PMC5495245
OTO - NOTNLM
OT  - *F-actin
OT  - *Zic2
OT  - *biomechanics
OT  - *mouse
OT  - *neural tube
COIS- The authors declare no conflict of interest.
EDAT- 2017/06/14 06:00
MHDA- 2018/05/10 06:00
CRDT- 2017/06/14 06:00
PHST- 2017/06/14 06:00 [pubmed]
PHST- 2018/05/10 06:00 [medline]
PHST- 2017/06/14 06:00 [entrez]
AID - 1700934114 [pii]
AID - 10.1073/pnas.1700934114 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2017 Jun 27;114(26):E5177-E5186. doi:
      10.1073/pnas.1700934114. Epub 2017 Jun 12.