REGIONAL DIFFERENCES IN MORPHOGENESIS OF THE NEUROEPITHELIUM SUGGEST MULTIPLE MECHANISMS OF SPINAL NEURULATION IN THE MOUSE

A study of neuroepithelial morphogenesis in the mouse embryo has ident ified three modes of neural tube formation that occur consecutively as neurulation progresses along the spinal region. The three modes of ne urulation differ in the extent to which the neuroepithelium exhibits f ormation of 'hinge points', i.e. localised bending owing to reduction in apical surface area. In Mode 1, bending occurs only in the neuroepi thelium overlying the notochord, creating a median hinge point. The ne ural folds remain straight along both apical and basal surfaces, resul ting in a neural tube with a slit-shaped lumen. In Mode 2, the neuroep ithelium forms paired dorsolateral hinge points, as well as a median h inge point, whereas the remaining portions of the neuroepithelium do n ot bend. This produces a neural tube with a diamond-shaped lumen. In M ode 3 neurulation, the entire neuroepithelium exhibits bending, so tha t the cells specific hinge points are not discernible; the resulting n eural tube has a circular lumen. The three modes of neurulation are pr esent in all three strains of mice studied: C57BL/6, CBA/Ca and curly tail, a mutant predisposed to neural tube defects. However, curly tail embryos exhibit a delay in transition from Mode 2 to Mode 3, precedin g faulty closure of the posterior neuropore. This heterogeneity of neu rulation morphogenesis in the mouse embryo indicates that the underlyi ng mechanisms may vary along the body axis. Specifically, we suggest t hat Mode 1 neurulation is driven largely by forces generated extrinsic to the neuroepithelium, in adjacent tissues, whereas Mode 3 neurulati on is dependent primarily on forces generated intrinsic to the neuroep ithelium. Down the body axis, there is a gradual decrease in the area of ectoderm involved in neural induction and, as neurulation reaches l ower spinal levels, the newly induced neural plate exhibits marked ind entation from the time of its first appearance. The transition from pr imary neurulation (neural folding of Mode 3 type) to secondary neurula tion (neural tube formation by cavitation) appears to be a smooth cont inuation of this trend, with loss of contact between the newly induced neuroepithelium and the outside of the embryo.