Kapron-Brás C M, Trasler D G
Department of Biology, McGill University, Montreal, Quebec, Canada.
Teratology. 1988 Apr;37(4):389-99. doi: 10.1002/tera.1420370412.
The splotch gene (Sp) and all-trans retinoic acid (RA) interact to cause spina bifida in mouse embryos. To investigate the mechanisms of action of the two, the spinal regions of Sp homozygotes, RA-treated wild-type, and control wild-type embryos were examined histologically by light microscopy on day 9 of gestation. The mean numbers of cells per section in the neural tube, mesoderm, and notochord were determined, along with the percentages of mitotic and pyknotic nuclei and the numbers of migrating neural crest cells. As well, the effect of Sp and RA on the extracellular matrix was studied histochemically with Alcian blue staining for glycosaminoglycans. The main defect in Sp homozygotes was a marked reduction in the number of migrating neural crest cells and the amount of extracellular matrix around the neural tube. Retinoic acid, on the other hand, caused a number of disruptions in the embryo, including abnormalities in the position of the notochord and the shape of the neural tube. Sp and RA delay neural tube closure and thus cause neural tube defects, through different mechanisms. However, the combined effects of the gene and teratogen on the embryo lead to a greater inhibition of neural tube closure than when either is present separately.
斑点基因（Sp）与全反式维甲酸（RA）相互作用，导致小鼠胚胎出现脊柱裂。为了研究二者的作用机制，在妊娠第9天，通过光学显微镜对Sp纯合子、经RA处理的野生型和对照野生型胚胎的脊柱区域进行组织学检查。测定了神经管、中胚层和脊索中每切片的平均细胞数，以及有丝分裂和固缩核的百分比和迁移神经嵴细胞的数量。此外，还用阿尔辛蓝染色法对糖胺聚糖进行组织化学研究，以探讨Sp和RA对细胞外基质的影响。Sp纯合子的主要缺陷是迁移神经嵴细胞数量显著减少以及神经管周围细胞外基质数量减少。另一方面，维甲酸会导致胚胎出现多种紊乱，包括脊索位置异常和神经管形状异常。Sp和RA通过不同机制延迟神经管闭合，从而导致神经管缺陷。然而，该基因和致畸剂对胚胎的联合作用比单独存在时对神经管闭合的抑制作用更大。
