背景:钙黏着蛋白是钙依赖性跨膜细胞-细胞粘附蛋白,是后生动物发育所必需的。它们由三个亚科组成:经典钙粘蛋白,它绑定了catenin,原钙粘蛋白,含有6-7个钙结合重复结构域,和非典型钙黏着蛋白。它们的功能包括形成粘附连接,建立平面细胞极性(PCP),调节细胞形状,扩散,和移民。因为它们是基底子宫造口术,棘皮动物为双边进化提供了重要的见解,但是他们唯一特征明确的钙黏着蛋白是G-钙黏着蛋白,由许多胚胎上皮表达的经典钙粘蛋白。我们旨在通过进行系统发育分析和检查紫癜发育过程中钙粘蛋白编码基因的时空表达模式来更好地表征棘皮动物钙粘蛋白。
结果:我们对两种类动物进行了系统发育分析,三颗小行星,一个海百合物种发现了十种棘皮动物钙粘蛋白,包括一个氘刀特定的直系同源物,cadherin-23和一种棘皮动物特异性的非典型cadherin,可能出现在棘齿小行星祖先中。发现dachsous-2直系同源物中的连环蛋白结合域是一种在小鼠中选择性丢失的氘管体特异性创新,而Fat4直向同源物中的那些似乎是Ambulacraria特异性的,并且在非海绵状棘皮动物中选择性丢失。已确定的棘皮动物钙粘蛋白缺乏脊椎动物特异性创新,但包含两种蛋白质,它们存在于原生动物中,而不存在于小鼠中。四种胚胎表达的钙黏着蛋白(脂肪非典型钙黏着蛋白1和4,dachsous-2和protcadherin-9)的时空表达模式是动态的,并反映了Frizzled5/8的表达模式,Frizzled5/8是一种非规范的WntPCP途径受体蛋白。
结论:棘皮动物钙黏着蛋白工具包更类似于古代双边早熟的原生动物和氘代细胞,而不是现存脊椎动物中发现的钙黏着蛋白套件。然而,似乎也有一些与钙黏着蛋白相关的创新。基于它们与PCP相关和肿瘤抑制蛋白相似的时空表达模式和直系同源关系,我们假设海胆钙黏着蛋白可能在调节胚胎上皮和器官的形状和生长中起作用。未来的实验将检查非类棘皮动物中钙粘蛋白的表达,并探索钙粘蛋白在棘皮动物发育过程中的功能。
BACKGROUND: Cadherins are calcium-dependent transmembrane cell-cell adhesion proteins that are essential for metazoan development. They consist of three subfamilies: classical cadherins, which bind catenin, protocadherins, which contain 6-7 calcium-binding repeat domains, and atypical cadherins. Their functions include forming adherens junctions, establishing planar cell polarity (PCP), and regulating cell shape, proliferation, and migration. Because they are basal deuterostomes, echinoderms provide important insights into bilaterian evolution, but their only well-characterized cadherin is G-cadherin, a classical cadherin that is expressed by many embryonic epithelia. We aimed to better characterize echinoderm cadherins by conducting phylogenetic analyses and examining the spatiotemporal expression patterns of cadherin-encoding genes during Strongylocentrotus purpuratus development.
RESULTS: Our phylogenetic analyses conducted on two echinoid, three asteroid, and one crinoid species identified ten echinoderm cadherins, including one deuterostome-specific ortholog, cadherin-23, and an echinoderm-specific atypical cadherin that possibly arose in an echinoid-asteroid ancestor. Catenin-binding domains in dachsous-2 orthologs were found to be a deuterostome-specific innovation that was selectively lost in mouse, while those in Fat4 orthologs appeared to be Ambulacraria-specific and were selectively lost in non-crinoid echinoderms. The identified suite of echinoderm cadherins lacks vertebrate-specific innovations but contains two proteins that are present in protostomes and absent from mouse. The spatiotemporal expression patterns of four embryonically expressed cadherins (fat atypical cadherins 1 and 4, dachsous-2, and
protocadherin-9) were dynamic and mirrored the expression pattern of Frizzled 5/8, a non-canonical Wnt PCP pathway receptor protein essential for archenteron morphogenesis.
CONCLUSIONS: The echinoderm cadherin toolkit is more similar to that of an ancient bilaterian predating protostomes and deuterostomes than it is to the suite of cadherins found in extant vertebrates. However, it also appears that deuterostomes underwent several cadherin-related innovations. Based on their similar spatiotemporal expression patterns and orthologous relationships to PCP-related and tumor-suppressing proteins, we hypothesize that sea urchin cadherins may play a role in regulating the shape and growth of embryonic epithelia and organs. Future experiments will examine cadherin expression in non-echinoid echinoderms and explore the functions of cadherins during echinoderm development.