Hunter K, Maden M, Summerbell D, Eriksson U, Holder N
Anatomy & Human Biology Group, King's College, Strand, London, United Kingdom.
Proc Natl Acad Sci U S A. 1991 May 1;88(9):3666-70. doi: 10.1073/pnas.88.9.3666.
There is increasing evidence that retinoic acid (RA), a vitamin A metabolite, plays a role in the development of the nervous system. Here we specifically test this notion by examining the effect of RA on neurite outgrowth from explanted segments of the axolotl spinal cord. We show that there is a threshold concentration in the region of 0.1-1 nM above which neurite outgrowth is stimulated 4-5 fold. Retinol, by contrast, only stimulated the migration of glial cells from the explants. Using HPLC we demonstrate that RA and retinol are present endogenously in the axolotl spinal cord. In addition, we have identified by immunocytochemistry with antipeptide antibodies the cells of the spinal cord that contain the binding proteins for RA (cellular RA-binding protein; CRABP) and retinol (cellular retinol-binding protein; CRBP). CRABP is found in the axons and CRBP is found in the ependyma and glial cells. These results provide strong evidence for a role for RA in the developing nervous system, and we propose a specific hypothesis involving CRBP, CRABP, retinol, and RA in the control of axon outgrowth in the spinal cord.
越来越多的证据表明，视黄酸（RA）作为维生素A的一种代谢产物，在神经系统发育中发挥作用。在此，我们通过检测RA对蝾螈脊髓外植体片段神经突生长的影响，专门对这一观点进行验证。我们发现，在0.1 - 1 nM范围内存在一个阈值浓度，高于此浓度，神经突生长会被刺激4 - 5倍。相比之下，视黄醇仅刺激了神经胶质细胞从外植体中迁移。通过高效液相色谱法（HPLC），我们证明了RA和视黄醇在蝾螈脊髓中内源性存在。此外，我们利用抗肽抗体通过免疫细胞化学方法鉴定出了脊髓中含有RA结合蛋白（细胞视黄酸结合蛋白；CRABP）和视黄醇结合蛋白（细胞视黄醇结合蛋白；CRBP）的细胞。CRABP存在于轴突中，而CRBP存在于室管膜和神经胶质细胞中。这些结果为RA在发育中的神经系统中发挥作用提供了有力证据，并且我们提出了一个涉及CRBP、CRABP、视黄醇和RA在脊髓轴突生长控制中的具体假说。
