Department of Anatomy & Cell Science, Kansai Medical University, Osaka 570-8506, Japan.
J Neurochem. 2010 Mar;112(5):1235-48. doi: 10.1111/j.1471-4159.2009.06536.x. Epub 2009 Dec 10.
C38 antigen is specifically expressed in neuronal cells of the retina. The purpose of this study was to isolate C38 cDNA and determine its molecular functions. Sequence analysis of C38 cDNA revealed that C38 is equivalent to rat BM88, which has been reported to induce cell-cycle arrest and neuronal differentiation in Neuro2a cells. C38 and Ki67, a marker of proliferating cells, were not colocalized during retinal development. C38 was first detected in the retinal ganglion cells at embryonic day 16, much later than the expression of doublecortin, a marker of immature neurons. Although all the horizontal cells were post-mitotic at this stage, C38 was not detected in horizontal cells until the postnatal period. In addition, C38 over-expression did not induce neuronal differentiation or cell-cycle arrest of pluripotent P19 embryonal carcinoma cells. Instead, C38 promoted maturation during neuronal differentiation of P19 embryonal carcinoma cells by down-regulating Oct-3, a pluripotent cell marker and enhancing the expressions of positive regulators of neurogenesis. In conclusion, during retinal development, C38 is first expressed in post-mitotic retinal neurons and is up-regulated during their maturation. C38 does not induce neuronal competence in pluripotent cells, but does promote maturation in already committed neuronal cells.
C38 抗原特异性表达于视网膜神经元细胞。本研究旨在分离 C38 cDNA 并确定其分子功能。C38 cDNA 的序列分析表明，C38 与大鼠 BM88 等同，BM88 已被报道可诱导 Neuro2a 细胞中的细胞周期停滞和神经元分化。在视网膜发育过程中，C38 与增殖细胞标志物 Ki67 不共定位。C38 于胚胎第 16 天首次在视网膜神经节细胞中检测到，明显晚于不成熟神经元标志物 doublecortin 的表达。尽管此时所有的水平细胞都已完成有丝分裂，但直到出生后阶段才在水平细胞中检测到 C38。此外，C38 的过表达并未诱导多能性 P19 胚胎癌细胞的神经元分化或细胞周期停滞。相反，C38 通过下调多能细胞标志物 Oct-3 并增强神经发生的正调控因子的表达，促进 P19 胚胎癌细胞向神经元分化的成熟。总之，在视网膜发育过程中，C38 首先在有丝分裂后视网膜神经元中表达，并在其成熟过程中上调。C38 不会诱导多能细胞的神经元潜能，但会促进已经定向的神经元细胞的成熟。
