Hot spots of retinoic acid synthesis in the developing spinal cord.

The embryonic spinal cord is known to be rich in retinoic acid, and several indirect lines of evidence point to a dorsoventral concentration difference of this compound. Previous measurements of dorsoventral retinoic acid levels, however, showed only minor differences. By a combination of microdissection and bioassay techniques, we compared retinoic acid levels with retinaldehyde dehydrogenase levels along spinal cords from early embryonic to postnatal mice. Both parameters vary in parallel, indicating that the principal reason for regional retinoic acid differences in the developing spinal cord is different levels of retinoic acid-generating enzyme. Consistent with previous reports, we observed overall quite high synthesis, decreasing with age, and no dorsoventral difference throughout much of the spinal cord length. In two locations, however, ventral synthesis exceeds dorsal synthesis by several orders of magnitude. These hot spots colocalize with the origins of the limb innervations. They are highest during early stages of limb innervation and disappear slowly postnatally. The synthesis hot spots are likely to create local retinoic acid diffusion halos, which may influence the survival of neurons in the limb regions of the spinal cord and which probably promote innervation of the developing limbs.