From Sheet to tube: Bioengineered Models of Neural Tube Defects

The neural tube, the precursor structure of the central nervous
system, forms from an initially-flat neuroepithelium, termed neural
plate, that folds and creates a tubular architecture. Progenitor cells
differentiate into distinct neural types and organize in discrete
domains as the neural tube bends. Neural tube formation generates
spatially heterogeneous stresses on progenitor cells, influencing
neural fate commitment. However, it is unknown how tissue
geometrical deformation affects patterning emergence and
morphogenesis. Here, we propose to impose mechanical forces on
epithelial neural progenitors to tralslate them form a planar to a
neural tube-like geometry. By using 3D-printed actuation devices and
morphogen sources, will deform a strip seeded with induced
pluripotent stem cells and create a new bioengineered model of
human neural tube development. This will allow to determine how
mechanical folding and tube size affect neural fate specification and
multiaxial patterning establishment. We will employ this biomimetic
model to assess how cells from patients with spina bifida, a defect of
neural tube closure, have impaired abilities in decoding mechanical
stimuli.