Syne2b/Nesprin-2 Is Required for Actin Organization and Epithelial Integrity During Epiboly Movement in Zebrafish

Abstract

Syne2b/nesprin-2 is a giant protein implicated in tethering the nucleus to the cytoskeleton and plays an important role in maintaining cellular architecture. Epiboly is a conserved morphogenetic movement that involves extensive spreading and thinning of the epithelial blastoderm to shape the embryo and organize the three germ layers. Dynamic cytoskeletal organization is critical for this process, but how it is regulated remains elusive. Here we generated a zebrafish syne2b mutant line and analyzed the effects of impaired Syne2b function during early development. By CRISPR/Cas9-mediated genome editing, we obtained a large deletion in the syne2b locus, predicted to cause truncation of the nuclear localization KASH domain in the translated protein. Maternal and zygotic syne2b embryos showed delayed epiboly initiation and progression without defects in embryonic patterning. Remarkably, disruption of Syne2b function severely impaired cytoskeletal organization across the embryo, leading to aberrant clustering of F-actin at multiple cell contact regions and abnormal cell shape changes. These caused disintegration of the epithelial blastoderm before the end of gastrulation in most severely affected embryos. Moreover, the migration of yolk nuclear syncytium also became defective, likely due to disorganized cytoskeletal networks at the blastoderm margin and in the yolk cell. These findings demonstrate an essential function of Syne2b in maintaining cytoskeletal architecture and epithelial integrity during epiboly movement.

Nuclear envelope, chromatin organizers, histones, and DNA: The many achilles heels exploited across cancers

“…Apart from biochemical cues, the nucleus directly perceives mechanical signals through the LINC complex, involving Nesprin and SUN proteins (Figure 2). Nesprins, which extend from the ONM to the perinuclear space, directly interact with cytoskeletal proteins such as vimentin, actin, and microtubules (Ketema et al, 2013;Gimpel et al, 2017;Li et al, 2021). Mechanical cues are subsequently propagated via the interaction with the SUN and KASH domain proteins (Starr and Fischer, 2005;Tzur et al, 2006).…”

The Adaptor Protein Lurap1 Is Required for Cell Cohesion during Epiboly Movement in Zebrafish

“…Moreover, actomyosin contractile rings are elaborated at the blastoderm margin during the late stages of epiboly [ 13 ]. These actin cytoskeletons are involved in coordinating the vegetal movement of both EVL and DEL [ 14 , 15 , 16 , 17 , 18 , 19 ], but how their organization is regulated in the embryo remains elusive.…”