McCaffery P, Dräger U C
Division of Developmental Neuroscience, E. K. Shriver Center, Waltham, MA 02254.
Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7194-7. doi: 10.1073/pnas.91.15.7194.
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.
已知胚胎脊髓富含视黄酸，并且有几条间接证据表明该化合物存在背腹浓度差异。然而，先前对视黄酸背腹水平的测量仅显示出微小差异。通过显微解剖和生物测定技术相结合，我们比较了从早期胚胎到出生后小鼠脊髓中视黄酸水平与视黄醛脱氢酶水平。这两个参数平行变化，表明发育中的脊髓中视黄酸区域差异的主要原因是视黄酸生成酶的水平不同。与先前的报道一致，我们观察到总体合成水平相当高，随年龄下降，并且在脊髓大部分长度上没有背腹差异。然而，在两个位置，腹侧合成比背侧合成高出几个数量级。这些热点与肢体神经支配的起源共定位。它们在肢体神经支配的早期阶段最高，出生后缓慢消失。合成热点可能会产生局部视黄酸扩散晕，这可能会影响脊髓肢体区域神经元的存活，并且可能促进发育中肢体的神经支配。
