Characterization of floor plate specific genes by using transgenic mice

点击翻译按钮获取中文摘要

Floor plate, a group of non-neural cells located in the ventral midline of the developing nervous system, plays an important role in neural patterning by secreting morphogens and axon guidance molecules. This study aims to clarify the functional significance of two floor plate specific genes, sulfatase FP1 (SulfFP1) and Autotaxin by using transgenic mice.SulfFP1 is a novel member of the sulfatase family, and is expressed in the floor plate, choroid plexus, bone-forming regions, kidney, some neurons in the adult brain. To characterize the regulatory element of SulfFP1 expression in these tissues, transgenic mice harboring the green fluorescent protein (GFP) under the control of the SulfFP1 promoter were generated. The 12 kbp genomic sequence upstream of the SulfFP1 transcription initiation site drives GFP expression in bone-formmg regions, kidney, and adult brain, but not in the floor plate and choroid plexus. Upstream 2.3 kbp sequence, but not 1.8 kbp sequence, drives the similar expression in the bone-formmg regions. The sequence between 1.8 kbp and 2.3 kbp includes the consensus sequence for the Sox-binding that is essential for bone development.Autotaxin, a member of the ecto-/exo-phosphodiesterase family, is initially identified as a cell motility promoting factor. It is recently reported to possess the lysophospholipase D activity that is required lysophophatidic acid production in the extracellular space, although its physiological role remains unknown. We therefore tried to generate transgenic mice that are overexpressing Autotaxin in the body, but only weakly-expressing lines were obtained. Slight increase of oligodendrocytes in the brain and spinal cord were observed in these lines. These results indicate that Autotaxin is involved in the oligodendrocyte differentiation, and that Autotaxin overexpression may lead to lethal phenotype in the early development.