XClose

UCL Great Ormond Street Institute of Child Health

Home

Great Ormond Street Institute of Child Health

Menu

Mechanisms of neurulation and NTDs

Our research aims to determine the mechanisms of neural tube closure at genetic, molecular, cellular, tissue and whole embryo levels of organisation.  In parallel, we are investigating a number of mouse models of NTD, to determine which aspects of the neural tube closure fails in each case.

This work can illuminate the normal embryonic process of neurulation, which is often considered a paradigm for morphogenesis in developing organisms.  It also offers insight into the ways in which neurulation can become disturbed leading to clinically important NTDs, including spina bifida and anencephaly.  By understanding how neurulation can be disturbed, we will be in a better position to develop new therapies to prevent human NTDs.


IN PREVIOUS WORK, THE NEURAL TUBE GROUP HAS:

Determined the developmental mechanisms responsible for regulating dorsolateral bending of the neural plate during spinal neurulation. This has revealed key roles for sonic hedgehog and BMP signalling (Ybot-Gonzalez et al, 2002; Ybot-Gonzalez et al, 2007).

Identified ventral-to-dorsal cell translocation within the neural plate during spinal closure, and provided evidence that dorsolateral bending may occur through localized 'buckling' of the neural plate at a transition point from low to high cell density (McShane et al, 2015).

Evaluated the role of programmed cell death (apoptosis) in neural tube closure. Surprisingly, we found that cell death, although plentiful at sites of neural tube closure, is not essential for closure to proceed (Massa et al, 2009).

Shown that actomyosin contraction is not required for mouse spinal neural tube closure, whereas precise regulation of apical F-actin assembly/disassembly in the neuroepithelium is a key requirement (Escuin et al, 2015).


Demonstrated that cellular protrusions, which make contact across the midline during neural fold fusion, arises from surface ectoderm cells and require Rac and Cdc42 GTPase function (Rolo et al, 2016).

Investigated the role of grainyhead-like genes in neural tube closure (further information).


  • CURRENT WORK INCLUDES:

  • Live-imaging and vital cell labelling to study the developmental lineage of the closing neural tube.
  • Biomechanics of neurulation