Expression of GDNF in metanephric mesenchyme

Glial cell line-derived neurotrophic factor (GDNF) is expressed in the metanephric mesenchyme during formation of the ureteric bud (inferred from mouse embryos). GDNF, which is secreted from the metanephric mesenchyme, interacts with the RET receptor tyrosine kinase on the nephric duct epithelium to regulate induction of the ureteric bud (inferred from mouse homologs). Mice lacking Gdnf fail to develop kidneys (Pichel et al. 1996). Based on phenotypes of gene knockouts in mice, Slit2 and Robo2 appear to repress Gdnf expression to limit the size of the ureteric bud (Grieshammer et al. 2004), however this may be an indirect effect produced by the activity of Slit2:Robo2 in producing normal physical separation of the mesenchyme from the Wolffian duct (mesonephric duct) and the ureteric epithelium (Wainwright et al. 2015). In mouse embryos, Foxc1 and Foxc2 from the paraxial mesoderm inhibit expression of Gdnf to limit the anterior extent of kidney development (Kume et al. 2000).

胶质细胞系来源的神经营养因子（GDNF）在输尿管芽形成过程中的生肾间充质中表达（据小鼠胚胎推断）。源自生肾间充质分泌的GDNF与肾管上皮上的RET受体酪氨酸激酶相互作用，以调节输尿管芽的诱导（据小鼠同源基因推断）。缺乏Gdnf基因的小鼠无法发育出肾脏（Pichel等，1996年）。根据小鼠基因敲除的表型，Slit2和Robo2似乎通过抑制Gdnf的表达来限制输尿管芽的大小（Grieshammer等，2004年），然而这可能是Slit2:Robo2活动产生的间接效应，该效应通过产生间充质与沃尔夫管（中肾管）及输尿管上皮的正常物理分离（Wainwright等，2015年）。在小鼠胚胎中，来自副轴中胚层的Foxc1和Foxc2抑制Gdnf的表达，以限制肾脏发育的前沿范围（Kume等，2000年）。