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家族（JAM family）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过程中已被充分阐明其功能，但目前对其在早期发育中的作用仍知之甚少。近期，我们在斑马鱼中证实了jamb与jamc基因在肌细胞融合中的功能。鉴于硬骨鱼谱系存在基因组复制事件，推测额外的JAM家族旁系同源基因或许也参与肌肉发育调控。为验证这一设想，我们通过检索斑马鱼基因组以鉴定潜在的旁系同源基因，并经序列比对确认了它们的同源性，最终将斑马鱼jam家族成员总数增至6个。随后，我们利用表面等离子体共振（surface plasmon resonance）技术比较了各旁系同源基因编码蛋白的物理结合特性，并检测了所有斑马鱼jam基因在不同发育阶段的基因表达模式。研究结果表明，相较于结合特异性，JAM-B与JAM-C的直系同源基因在结合强度与基因表达模式上发生了显著的亚功能化。jamb2与jamc2这两个旁系同源基因未在野生型胚胎的体节或肌节中被检出。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。