Starz-Gaiano M, Cho N K, Forbes A, Lehmann R
Howard Hughes Medical Institute, Developmental Genetics Program, Skirball Institute at NYU Medical School, New York, NY 10016, USA.
Development. 2001 Mar;128(6):983-91. doi: 10.1242/dev.128.6.983.
Temporal and spatial controls of cell migration are crucial during normal development and in disease. Our understanding, though, of the mechanisms that guide cells along a specific migratory path remains largely unclear. We have identified wunen 2 as a repellant for migrating primordial germ cells. We show that wunen 2 maps next to and acts redundantly with the previously characterized gene wunen, and that known wunen mutants affect both transcripts. Both genes encode Drosophila homologs of mammalian phosphatidic acid phosphatase. Our work demonstrates that the catalytic residues of Wunen 2 are necessary for its repellant effect and that it can affect germ cell survival. We propose that spatially restricted phospholipid hydrolysis creates a gradient of signal necessary and specific for the migration and survival of germ cells.
细胞迁移的时空控制在正常发育和疾病过程中至关重要。然而,我们对引导细胞沿着特定迁移路径的机制仍知之甚少。我们已确定无翅蛋白2(wunen 2)是迁移的原始生殖细胞的排斥因子。我们发现,wunen 2基因定位于先前已鉴定的基因无翅蛋白(wunen)附近,并与其发挥冗余作用,而且已知的无翅蛋白突变体会影响这两个基因的转录本。这两个基因都编码哺乳动物磷脂酸磷酸酶的果蝇同源物。我们的研究表明,无翅蛋白2的催化残基对其排斥作用是必需的,并且它会影响生殖细胞的存活。我们认为,空间受限的磷脂水解作用会产生一种对生殖细胞迁移和存活所必需且特定的信号梯度。