Dynamic Assembly of Brambleberry Mediates Nuclear Envelope Fusion during Early Development

To accommodate the large cells following zygote formation, early blastomeres employ modified cell divisions. Karyomeres are one such modification, mitotic intermediates wherein individual chromatin masses are surrounded by nuclear envelope; the karyomeres then fuse to form a single mononucleus. We identified brambleberry, a maternal-effect zebrafish mutant that disrupts karyomere fusion, resulting in formation of multiple micronuclei. As karyomeres form, Brambleberry protein localizes to the nuclear envelope, with prominent puncta evident near karyomere-karyomere interfaces corresponding to membrane fusion sites. brambleberry corresponds to an unannotated gene with similarity to Kar5p, a protein that participates in nuclear fusion in yeast. We also demonstrate that Brambleberry is required for pronuclear fusion following fertilization in zebrafish. Our studies provide insight into the machinery required for karyomere fusion and suggest that specialized proteins are necessary for proper nuclear division in large dividing blastomeres. [Display omitted] ► Brambleberry (Bmb) promotes nuclear envelope fusion of karyomeres ► Bmb assembles into foci, marking future and active karyomere fusion site ► Loss of maternal Bmb causes multiple micronuclei to form in cleavage stage cells ► Bmb acts in pronuclear fusion during zygote formation following fertilization During early embryogenesis when cells are large, individual chromatin masses are first encased by nuclear envelope, forming karyomeres that then fuse into a nucleus. A forward-genetics approach identifies a new nuclear envelope protein, Brambleberry, that dynamically assembles into foci that mediate karyomere fusion in zebrafish.