Leimeister Cornelia, Steidl Christian, Schumacher Nina, Erhard Sabine, Gessler Manfred
Theodor-Boveri-Institute, Physiological Chemistry I, University of Wuerzburg, 97074, Wuerzburg, Germany.
Dev Biol. 2002 Sep 15;249(2):204-18. doi: 10.1006/dbio.2002.0764.
Kidney development has often served as a model for epithelial-mesenchymal cell interaction where the branching epithelium of the ureteric bud induces the metanephrogenic mesenchyme to form epithelial nephrons. In a screen for genes differentially expressed during kidney development, we have identified a novel gene that is dynamically expressed in the branching ureter and the developing nephrons. It was designated Emu1 since it shares an N-terminal cysteine-rich domain with Emilin1/2 and Multimerin. This highly conserved EMI domain is also found in another novel protein (Emu2) of similar protein structure: an N-terminal signal peptide followed by the EMI domain, an interrupted collagen stretch, and a conserved C-terminal domain of unknown function. We identified two further secreted EMI domain proteins, prompting us to compare their gene and protein structures, the EMI domain phylogeny, as well as the embryonic expression pattern of known (Emilin1/2, Multimerin) and novel (Emu1/2, Emilin3, Multimerin2) Emu gene family members. Emu1 and Emu2 not only show a similar structural organization, but furthermore a striking complementary expression in organs developing through epithelial-mesenchymal interactions. In these tissues, Emu1 is restricted to epithelial and Emu2 to mesenchymal cells. Preliminary biochemical analysis of Emu1/2 confirmed that they are secreted glycoproteins which are attached to the extracellular matrix and capable of forming homo- and heteromers via disulfide bonding. The widespread, but individually distinct expression patterns of all Emu gene family members suggest multiple functions during mouse embryogenesis. Their multidomain protein structure may indicate that Emu proteins interact with several different extracellular matrix components and serve to connect and integrate the function of multiple partner molecules.
肾脏发育常被用作上皮-间充质细胞相互作用的模型，其中输尿管芽的分支上皮诱导后肾间充质形成上皮性肾单位。在一项针对肾脏发育过程中差异表达基因的筛选中，我们鉴定出一个新基因，它在分支输尿管和发育中的肾单位中动态表达。它被命名为Emu1，因为它与Emilin1/2和Multimerin共享一个富含N端半胱氨酸的结构域。在另一种具有相似蛋白质结构的新蛋白质（Emu2）中也发现了这种高度保守的EMI结构域：一个N端信号肽，接着是EMI结构域、一个中断的胶原蛋白延伸段，以及一个功能未知的保守C端结构域。我们又鉴定出另外两种分泌型EMI结构域蛋白，这促使我们比较它们的基因和蛋白质结构、EMI结构域系统发育，以及已知（Emilin1/2、Multimerin）和新发现（Emu1/2、Emilin3、Multimerin2）的Emu基因家族成员的胚胎表达模式。Emu1和Emu2不仅显示出相似的结构组织，而且在通过上皮-间充质相互作用发育的器官中表现出惊人的互补表达。在这些组织中，Emu1局限于上皮细胞，Emu2局限于间充质细胞。对Emu1/2的初步生化分析证实它们是分泌型糖蛋白，附着于细胞外基质，并且能够通过二硫键形成同源和异源多聚体。所有Emu基因家族成员广泛但各自独特的表达模式表明它们在小鼠胚胎发育过程中具有多种功能。它们的多结构域蛋白质结构可能表明Emu蛋白与几种不同的细胞外基质成分相互作用，并有助于连接和整合多个伙伴分子的功能。
