Genomic Organisation, Embryonic Expression and Biochemical Interactions of the Zebrafish Junctional Adhesion Molecule Family of Receptors

The mammalian JAM family is composed of three cell surface receptors. Interactions between the proteins have well-characterised roles in inflammation and tight junction formation, but little is known about their function in early development. Recently, we identified a role for jamb and jamc in zebrafish myocyte fusion. Genome duplication in the teleost lineage raised the possibility that additional JAM family paralogues may also function in muscle development. To address this, we searched the zebrafish genome to identify potential paralogues and confirmed their homology, bringing the total number of zebrafish jam family members to six. We then compared the physical binding properties of each paralogue by surface plasmon resonance and determined the gene expression patterns of all zebrafish jam genes at different stages of development. Our results suggest a significant sub-functionalisation of JAM-B and JAM-C orthologues with respect to binding strength (but not specificity) and gene expression. The paralogous genes, jamb2 and jamc2, were not detected in the somites or myotome of wild-type embryos. We conclude that it is unlikely that the paralogues have a function in primary myogenesis.

哺乳动物JAM（Junctional Adhesion Molecule）家族由三类细胞表面受体构成。该家族蛋白间的相互作用在炎症反应与紧密连接形成中具有明确的功能，但学界对其在早期发育过程中的作用仍知之甚少。近期，我们在斑马鱼肌细胞融合过程中鉴定出了jamb与jamc的相关功能。硬骨鱼谱系所发生的基因组复制事件，提示可能存在额外的JAM家族旁系同源基因，且这类基因或许也参与肌肉发育过程。为探究这一科学问题，我们对斑马鱼基因组进行检索以鉴定潜在的旁系同源基因，并验证了它们的同源性，最终将斑马鱼jam家族成员总数确定为6个。随后，我们通过表面等离子体共振技术比较了各旁系同源基因的物理结合特性，并测定了斑马鱼所有jam基因在不同发育阶段的基因表达模式。研究结果表明，JAM-B与JAM-C的直系同源基因在结合强度（而非结合特异性）与基因表达层面发生了显著的亚功能化现象。在野生型胚胎的体节与肌节中，并未检测到旁系同源基因jamb2与jamc2的表达。综上，我们认为这些旁系同源基因不太可能在原发性肌发生过程中发挥功能。