Cephalic neurulation in the mouse embryo analyzed by SEM and morphometry.

A detailed account of mouse neurulation is given based mostly on SEM analysis over 20 hr of development. Many observations and measurements were made on staged living embryos and on embryos prepared for scanning and light microscopy to help deduce what mechanisms may contribute to neural tube formation. Each lateral half of the early cephalic neural plate makes a convex bulge, opposite to the way it must fold to form a tube. Underlying mesenchyme and matrix are reported to have a role in forming these bulges. Processes that form the tube must overcome this opposed folding and the forces that produce it. Cranial flexure begins long before tube formation. The flexure commences at the rostra1 tip of the cephalic neural plate, then the apex of the flexure migrates caudally to the mesencephalic region. Early appearance of this flexure imposes a mechanical impediment to tube closure in forebrain and midbrain regions. Tube closure begins in the cervical region exactly where the neural plate is reflected dorsally by a bend in the embryo. This bend may mechanically assist closure in this region. Cells of the mouse neural plate are reported to contain organized microfilaments and microtubules, and the plate cells appear to change shape (reduce apical area and increase cell height) in the same manner as that suggested in embryos of some other species to contribute to neural tube formation. Measurements show that the lateral edges of the cephalic neural plate elongate craniocaudally more than the midline of the plate through each period. This elongation could contribute to the folding of the plate into a tube. The progress of cranial ventral flexure pauses while tube formation occurs, but edge elongation continues, presumably contributing to tube formation. There is considerable increase in volume of the neural plate during tube closure, and cell proliferation and enlargement of daughter cells seem sufficient to account for this growth. Mitotic spindles are positioned to place the majority of the daughter cells into the long axis of the neural plate, so ordered growth may be the main mechanism of elongation of the plate in the craniocaudal direction, which in turn may assist in tube formation. Mouse cephalic neural plates appear overlying already segmented cranial mesenchyme according to previous reports, and neuromeres develop precociously in the open plates, where their positions correlate exactly with the underlying segmented mesenchyme. Some features of neurulation in the mouse embryo have already been elucidated, and there is agreement on its general course. During presomite stages, the cephalic neural plate is present and thickening, but the more caudal neural plate is yet to be formed (Waterman, 1976). Each lateral half of the early cephalic plate makes a convex bulge (Morriss and Solursh, 1978a, 1978b). This convex bilateral bulging is in the direction opposite the concave bending that later forms the tube. Neural tube formation begins in the cervical region, but fusion of the neural folds in the embryos of several rodents, including the mouse, occurs at more than one site (Waterman, 1976; Geelen and Langman, 1977; Kaufman, 1979; Morriss and New, 1979), and in this respect differs from the human embryo (Kaufman, 1979; O’Rahilly and Gardner, 1971,1979). From the cervical region, fusion proceeds both rostrally and