Cellular mechanisms underlying the morphogenetic biomechanics of mammalian neural tube closure (360G-Wellcome-211112_Z_18_Z)
Primary neurulation is a biomechanical process whereby the flat neural plate folds into a closed neural tube (NT). Closure initiates at the hindbrain/cervical boundary and "zippers" bi-directionally to form the cephalic and spinal NT. Failure of NT closure results in defects including spina bifida, which continue to affect 1:1,000 pregnancies. Despite advances in delineating its genetic control, we lack an integrated understanding of neurulation as a biomechanical morphogenetic process. To this end I have combined mouse posterior neuropore (PNP) live-imaging, laser ablation, and novel strain-mapping workflows to describe the tissue-level biomechanics of spinal closure. These revealed that the PNP is biomechanically coupled by a far-reaching actomyosin network, identified teratogenic/genetic models in which altered PNP biomechanics predict spina bifida, and identified a novel closure-initiation point ("Closure 5") which forms at the embryo’s caudal extreme. We now propose to determine: Are mechanical forces which promote and oppose NT closure balanced through actomyosin-dependent contractility overcoming tissue rigidity, up to a failure threshold? Do biomechanical differences between spinal and cephalic closure account for the latter’s apparent predisposition to failure? Does Closure 5 formation critically facilitate completion of spinal neural tube closure in humans and mice, and how is its morphogenesis regulated?
Where is this data from?
This data was originally published by The Wellcome Trust. If you see something about your organisation or the funding it has received on this page that doesn't look right you can submit a grantee amendment request. You can hover over codes from standard codelists to see the user-friendly name provided by 360Giving.
Grant Details
Amount Awarded | 1101901 |
Applicant Surname | Galea |
Approval Committee | Clinical Interview Committee |
Award Date | 2018-05-23T00:00:00+00:00 |
Financial Year | 2017/18 |
Grant Programme: Title | Clinical Research Career Development Fellowship |
Internal ID | 211112/Z/18/Z |
Lead Applicant | Dr Gabriel Galea |
Partnership Value | 1101901 |
Planned Dates: End Date | 2024-10-01T00:00:00+00:00 |
Planned Dates: Start Date | 2018-10-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |
Sponsor(s) | Prof Andrew Copp |