The role of the mesenchyme in cranial neural fold elevation.

The basic aim of this research was to examine the role of the mesenchyme in cranial neural fold elevation. It has been previously postulated that the expansion of an hyaluronate-rich extracellular matrix in the fold mesenchyme is responsible for neural fold elevation. In this study we provide evidence that such expansion may play an important role in cranial neural fold elevation by pushing the folds towards the dorsal midline to assist in their elevation. For mesenchymal expansion to result in fold elevation, hyaluronate (HA) and mesenchymal cells must be non-r and omly distributed within the mesenchyme. Patterns of mesenchymal cell distribution and cell proliferation were analyzed using the computer-assisted method of smoothed spatial averaging. The distribution of Alcian blue-stained and $\\sp3$H-glucosamine-labelled HA was also analyzed during cranial neural fold elevation using established image processing techniques. Our results showed that mesenchymal cells and HA were found in a non-r and om distribution within the mesenchyme and showed distinct temporal and spatial patterns of distribution which could be correlated with stages of neural fold elevation. Elevation was accompanied by significant mesenchymal expansion and with decreased mesenchymal cell density and HA concentration in the central mesenchyme. Analysis of the distribution of $\\sp3$H-thymidine-labelled mesenchymal cells indicated that differential mitotic activity was not responsible for decreased mesenchymal cell density. Likewise, analysis of distribution patterns of $\\sp3$H-glucosamine-labelled HA indicated that decreased HA concentration was not produced by regional differences in HA synthesis. These results suggest that decreases in mesenchymal cell density and HA concentration that occur during neural fold elevation are produced by mesenchymal expansion. When mesenchymal expansion was inhibited by exposure to diazo-oxo-norleucine (DON) which interferes with HA synthesis, the cranial neural folds failed to elevate. Analysis of distribution patterns of labelled and unlabelled mesenchymal cells indicated that in treated folds regional differences in mesenchymal cell density were produced by differential mitotic rates. Analysis of Alcian blue-stained and $\\sp3$H-glucosamine-labelled HA distribution patterns showed that HA synthesis was decreased in treated folds. Patterns resembled those of control folds prior to mesenchymal expansion and fold elevation.Ph.D.MorphologyUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/162099/1/8907107.pd