Suzanne M, Irie K, Glise B, Agnès F, Mori E, Matsumoto K, Noselli S
Centre de Biologie du Développement, UMR5547 Centre National de la Recherche Scientifique (CNRS), 31062 Toulouse Cedex, France.
Genes Dev. 1999 Jun 1;13(11):1464-74. doi: 10.1101/gad.13.11.1464.
In mammalian cells, the p38 mitogen-activated protein kinase (MAPK) pathway is activated in response to a variety of environmental stresses and inflammatory stimuli. However, the role of p38 MAPK signaling in unchallenged conditions remains largely unknown. We have isolated mutations in a Drosophila p38 MAPKK gene homolog, licorne (lic), and show that during oogenesis, lic is required in the germ line for correct asymmetric development of the egg. In lic mutant egg chambers, oskar mRNA posterior localization is not properly maintained, resulting in anteroposterior patterning defects in the embryo. Furthermore, lic loss-of-function in the germ line leads to reduced EGF receptor activity in dorsal follicle cells and ventralization of the egg shell. Both these defects are associated with a diminution of gurken protein levels in the oocyte. Our phenotypic data argue for a role of lic in a post-transcriptional regulation of the grk gene. Furthermore, they show that in addition to the well-characterized Ras/Raf/ERK MAPK pathway acting in the follicle cells, another related signaling cascade, the p38 MAPK pathway, is required in the germ line for correct axes determination. These results provide the first genetic demonstration of an essential function for a p38 pathway during development.
在哺乳动物细胞中,p38丝裂原活化蛋白激酶(MAPK)通路会因多种环境应激和炎症刺激而被激活。然而,p38 MAPK信号在未受刺激条件下的作用仍 largely未知。我们在果蝇p38 MAPKK基因同源物licorne(lic)中分离出了突变,并表明在卵子发生过程中,lic在生殖系中是卵子正确不对称发育所必需的。在lic突变的卵室中,oskarmRNA的后部定位不能正常维持,导致胚胎前后轴模式形成缺陷。此外,生殖系中lic功能的丧失导致背侧卵泡细胞中表皮生长因子受体活性降低以及卵壳腹侧化。这两种缺陷都与卵母细胞中gurken蛋白水平的降低有关。我们的表型数据表明lic在grk基因的转录后调控中起作用。此外,它们还表明,除了在卵泡细胞中起作用的已充分表征的Ras/Raf/ERK MAPK通路外,生殖系中还需要另一个相关的信号级联反应,即p38 MAPK通路来正确确定轴。这些结果首次通过遗传学证明了p^{38}通路在发育过程中的重要功能。