Biology subjects

McNeely, K. C.

Publications and source records attributed to McNeely, K. C..

4 recordsLinked to original sources

bioRxiv2025

Cytokinetic abscission failures in a polarized epithelium affect apical membrane size and cilia

Cytokinetic abscission is the last step of cell division, during which the intercellular bridge between daughter cells is severed. While abscission genes are linked to cancers and developmental disorders, the consequences of disrupted abscission in vivo have remained under-explored. For a polarized epithelium to expand or renew, cells within it must divide while maintaining polarity, cell junctions, and epithelial integrity. They undergo a polarized form of cytokinesis in which abscission occurs at the apical membrane. Here, we investigate how stochastic abscission failures in a polarized epithelium disrupt epithelial architecture, using mouse neuroepithelium as a model. Previously we showed that in the forebrain of Cep55 knockout (KO) mouse embryos, a subset of neuroepithelial stem cells (NSCs) fail abscission and become binucleate, and some of those undergo p53-mediated apoptosis. Here we use the Cep55 KO forebrain to focus on how disrupting abscission in a polarized epithelium affects the apical membrane structure. We find that NSCs in Cep55 KO neuroepithelium have preserved epithelial polarity and integrity. However, they have enlarged apical membranes (called apical endfeet), longer primary cilia, and increased bi-ciliation. We test whether the enlarged apical endfeet arise from filling the space of apoptotic neighbors. However, blocking apoptosis does not rescue but exacerbates the phenotypes: extra-large apical endfeet have further increased multi-ciliation, supernumerary centrosomes, and abnormal or multiple nuclei. These findings show the importance of proper abscission in a polarized epithelium to maintain epithelial structure, and the need for p53-mediated apoptosis to protect the tissue in the face of stochastic abscission failures.

cell biology↗

bioRxiv2020

Loss of coiled-coil protein Cep55 impairs abscission processes and results in p53-dependent apoptosis in developing cortex

To produce a brain of normal size and structure, embryonic neural stem cell (NSCs) must tightly regulate their cell divisions. Cerebral cortex NSCs undergo a polarized form of cytokinesis whose regulation is poorly understood. Cytokinetic abscission severs the daughter cells and is mediated by the midbody at the apical membrane. Here we elucidate the role of the coiled-coil midbody protein Cep55 in NSC abscission and brain development. A knockout of Cep55 in mice causes microcephaly with reduced NSCs and neurons, but relatively normal body size. Fixed and live analyses show NSCs lacking Cep55 have decreased but not eliminated ESCRT recruitment, and have abnormal abscission and higher rates of failure. P53-mediated apoptosis is greatly increased in the brain, but not other tissues, and p53 knockout partly rescues brain size. Thus, loss of Cep55 causes abscission defects and failures in multiple cell types, but the secondary p53 response and apoptosis is brain-specific.

developmental biology↗

bioRxiv2019

Cytokinetic furrowing and abscission dynamics during brain development revealed by live imaging

McNeely et al. quantitatively analyze polarized cytokinetic furrow ingression and abscission in mouse neuroepithelium by live imaging. The findings show important differences from HeLa cells, and suggest abscission timing and midbody release may be developmentally regulated, to influence daughter cell fate during brain growth. AbstractWhile mechanisms of cytokinesis have been identified in single cell models, the spatial and temporal regulation in developing tissues is less understood. Here we compare cytokinetic furrowing and abscission in mouse neuroepithelial stem cells (NESCs) at different developmental stages and in a cytokinesis mutant, including imaging abscission dynamics in a polarized epithelium for the first time. We find that asymmetric furrows of NESCs ingress at a constant but slow rate, and form the midbody at the apical membrane. Usually, bilateral abscission on each midbody flank releases the midbody remnant extracellularly. Interestingly, midbody remnants are more associated with early proliferative divisions. Unexpectedly, in the microcephalic Kif20b mutant, abscission is accelerated and occurs when the midbody is wider. The daughter cells of mutant NESCs show increased cell cycle exit that is p53-independent. We suggest that abscission mechanisms are developmentally regulated. These results provide significant insight into adaptations of a fundamental cell biological process required for proper brain growth.

developmental biology↗

bioRxiv2017

Kinesin-6 KIF20B is required for efficient cytokinetic furrowing and timely abscission in human cells

Cytokinesis requires the cooperation of many cytoskeletal and membrane regulators. Most of the major players required for cytokinesis are known, but the temporal regulation and adaptations for different cell types are less understood. KIF20B (previously called MPHOSPH1 or MPP1) is a member of the Kinesin-6 family, which also includes the better-known members KIF23/MKLP1 and KIF20A/MKLP2. Previously, we showed that mouse Kif20b is involved in cerebral cortex growth and midbody organization of neural stem cells. Here we show that KIF20B has a cell-autonomous role in cytokinesis in isolated human cells. It localizes to microtubules of the central spindle and midbody throughout cytokinesis, at sites distinct from the other Kinesin-6 family members. KIF20B is not required for central spindle or midbody assembly, but affects midbody shape and late maturation steps. KIF20B appears to temporally regulate both furrow ingression and abscission.

cell biology↗