Cookies disclaimer

I agree Our site saves small pieces of text information (cookies) on your device in order to deliver better content and for statistical purposes. You can disable the usage of cookies by changing the settings of your browser. By browsing our website without changing the browser settings you grant us permission to store that information on your device.

Cellular mechanisms underlying the morphogenetic biomechanics of mammalian neural tube closure (360G-Wellcome-211112_Z_18_A)

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?


30 Sep 2018

Grant details
Amount Awarded 25000
Applicant Surname Galea
Approval Committee Internal Decision Panel
Award Date 2018-09-30T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Clinical Research Career Development Fellowship
Internal ID 211112/Z/18/A
Lead Applicant Dr Gabriel Galea
Planned Dates: End Date 2023-09-30T00:00:00+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
Additional data added by GrantNav