Department of Biology, University of Virginia, Charlottesville, VA, USA.
Department of Biology, University of Virginia, Charlottesville, VA, USA.
Dev Biol. 2021 Aug;476:314-327. doi: 10.1016/j.ydbio.2021.04.007. Epub 2021 Apr 29.
Adhesive interactions are essential for tissue patterning and morphogenesis yet difficult to study owing to functional redundancies across genes and gene families. A useful system in which to dissect roles for cell adhesion and adhesion-dependent signaling is the pattern formed by pigment cells in skin of adult zebrafish, in which stripes represent the arrangement of neural crest derived melanophores, cells homologous to melanocytes. In a forward genetic screen for adult pattern defects, we isolated the pissarro (psr) mutant, having a variegated phenotype of spots, as well as defects in adult fin and lens. We show that psr corresponds to junctional adhesion protein 3b (jam3b) encoding a zebrafish orthologue of the two immunoglobulin-like domain receptor JAM3 (JAM-C), known for roles in adhesion and signaling in other developing tissues, and for promoting metastatic behavior of human and murine melanoma cells. We found that zebrafish jam3b is expressed post-embryonically in a variety of cells including melanophores, and that jam3b mutants have defects in melanophore survival. Jam3b supported aggregation of cells in vitro and was required autonomously by melanophores for an adherent phenotype in vivo. Genetic analyses further indicated both overlapping and non-overlapping functions with the related receptor, Immunoglobulin superfamily 11 (Igsf11) and Kit receptor tyrosine kinase. These findings suggest a model for Jam3b function in zebrafish melanophores and hint at the complexity of adhesive interactions underlying pattern formation.
黏附相互作用对于组织模式形成和形态发生至关重要,但由于基因和基因家族之间存在功能冗余,因此难以研究。一个有用的系统,可以剖析细胞黏附和黏附依赖性信号在成年斑马鱼皮肤中色素细胞形成的模式中的作用,其中条纹代表神经嵴衍生的黑素细胞的排列,这些细胞与黑素细胞同源。在针对成年模式缺陷的正向遗传筛选中,我们分离出了 pissarro (psr) 突变体,其表现为斑驳的表型,还存在成年鳍和晶状体的缺陷。我们表明,psr 对应于连接黏附蛋白 3b (jam3b),它编码斑马鱼 JAM3(JAM-C)的两个免疫球蛋白样结构域受体的同源物,已知在其他发育组织中的黏附和信号传导中起作用,并促进人类和鼠黑色素瘤细胞的转移行为。我们发现斑马鱼 jam3b 在胚胎后表达在各种细胞中,包括黑素细胞,并且 jam3b 突变体在黑素细胞的存活中存在缺陷。Jam3b 在体外支持细胞的聚集,并且在体内对于黑素细胞的黏附表型是自主需要的。遗传分析进一步表明,与相关受体免疫球蛋白超家族 11 (Igsf11) 和 Kit 受体酪氨酸激酶具有重叠和非重叠的功能。这些发现表明了 Jam3b 在斑马鱼黑素细胞中的功能模型,并暗示了模式形成的基础下黏附相互作用的复杂性。