Wenzhe Li

All Publications

• Inward transport of organelles drives outward migration of the spindle during C. elegans meiosis. Cell reports Aquino, A. P., Li, W., Lele, A., Lazureanu, D., Hampton, M. F., Do, R. M., Lafrades, M. C., Barajas, M. G., Batres, A. A., McNally, F. J. 2025; 44 (4): 115458

  Abstract

  Cortical positioning of the meiotic spindle within an oocyte is required to expel chromosomes into polar bodies to generate a zygote with the correct number of chromosomes. In C. elegans, yolk granules and mitochondria are packed inward, away from the cortex, while the spindle moves outward, both in a kinesin-dependent manner. The kinesin-dependent inward packing of yolk granules suggests the existence of microtubules with minus ends at the cortex and plus ends extending inward, making it unclear how kinesin moves the spindle outward. We hypothesize that the inward packing of organelles might indirectly force the spindle outward by volume exclusion. To test this hypothesis, we generate a strain in which the only kinesin consists of motor domains with no cargo-binding tail optogenetically attached to mitochondria. This mitochondria-only kinesin packs mitochondria into a tight ball and efficiently moves the meiotic spindle to the cortex, supporting the volume exclusion hypothesis.

  View details for DOI 10.1016/j.celrep.2025.115458

  View details for PubMedID 40121661

  View details for PubMedCentralID PMC12077383

• Redundant microtubule crosslinkers prevent meiotic spindle bending to ensure diploid offspring in <i>C</i>. <i>elegans</i> PLOS GENETICS Li, W., Crellin, H. A., Cheerambathur, D., Mcnally, F. J. 2023; 19 (12): e1011090

  Abstract

  Oocyte meiotic spindles mediate the expulsion of ¾ of the genome into polar bodies to generate diploid zygotes in nearly all animal species. Failures in this process result in aneuploid or polyploid offspring that are typically inviable. Accurate meiotic chromosome segregation and polar body extrusion require the spindle to elongate while maintaining its structural integrity. Previous studies have implicated three hypothetical activities during this process, including microtubule crosslinking, microtubule sliding and microtubule polymerization. However, how these activities regulate spindle rigidity and elongation as well as the exact proteins involved in the activities remain unclear. We discovered that C. elegans meiotic anaphase spindle integrity is maintained through redundant microtubule crosslinking activities of the Kinesin-5 family motor BMK-1, the microtubule bundling protein SPD-1/PRC1, and the Kinesin-4 family motor, KLP-19. Using time-lapse imaging, we found that single depletion of KLP-19KIF4A, SPD-1PRC1 or BMK-1Eg5 had minimal effects on anaphase B spindle elongation velocity. In contrast, double depletion of SPD-1PRC1 and BMK-1Eg5 or double depletion of KLP-19KIF4A and BMK-1Eg5 resulted in spindles that elongated faster, bent in a myosin-dependent manner, and had a high rate of polar body extrusion errors. Bending spindles frequently extruded both sets of segregating chromosomes into two separate polar bodies. Normal anaphase B velocity was observed after double depletion of KLP-19KIF4A and SPD-1PRC1. These results suggest that KLP-19KIF4A and SPD-1PRC1 act in different pathways, each redundant with a separate BMK-1Eg5 pathway in regulating meiotic spindle elongation. Depletion of ZYG-8, a doublecortin-related microtubule binding protein, led to slower anaphase B spindle elongation. We found that ZYG-8DCLK1 acts by excluding SPD-1PRC1 from the spindle. Thus, three mechanistically distinct microtubule regulation modules, two based on crosslinking, and one based on exclusion of crosslinkers, power the mechanism that drives spindle elongation and structural integrity during anaphase B of C.elegans female meiosis.

  View details for DOI 10.1371/journal.pgen.1011090

  View details for Web of Science ID 001143489200004

  View details for PubMedID 38150489

  View details for PubMedCentralID PMC10775986

• Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein NATURE COMMUNICATIONS Okada, K., Iyer, B. R., Lammers, L. G., Gutierrez, P. A., Li, W., Markus, S. M., Mckenney, R. J. 2023; 14 (1): 5833

  Abstract

  Processive transport by the microtubule motor cytoplasmic dynein requires the regulated assembly of a dynein-dynactin-adapter complex. Interactions between dynein and dynactin were initially ascribed to the dynein intermediate chain N-terminus and the dynactin subunit p150Glued. However, recent cryo-EM structures have not resolved this interaction, questioning its importance. The intermediate chain also interacts with Nde1/Ndel1, which compete with p150Glued for binding. We reveal that the intermediate chain N-terminus is a critical evolutionarily conserved hub that interacts with dynactin and Ndel1, the latter of which recruits LIS1 to drive complex assembly. In additon to revealing that the intermediate chain N-terminus is likely bound to p150Glued in active transport complexes, our data support a model whereby Ndel1-LIS1 must dissociate prior to LIS1 being handed off to dynein in temporally discrete steps. Our work reveals previously unknown steps in the dynein activation pathway, and provide insight into the integrated activities of LIS1/Ndel1 and dynactin/cargo-adapters.

  View details for DOI 10.1038/s41467-023-41466-5

  View details for Web of Science ID 001079212000027

  View details for PubMedID 37730751

  View details for PubMedCentralID PMC10511499

• Cohesin is required for meiotic spindle assembly independent of its role in cohesion in <i>C</i>. <i>elegans</i> PLOS GENETICS McNally, K. P., Beath, E. A., Danlasky, B. M., Barroso, C., Gong, T., Li, W., Martinez-Perez, E., McNally, F. J. 2022; 18 (10): e1010136

  Abstract

  Accurate chromosome segregation requires a cohesin-mediated physical attachment between chromosomes that are to be segregated apart, and a bipolar spindle with microtubule plus ends emanating from exactly two poles toward the paired chromosomes. We asked whether the striking bipolar structure of C. elegans meiotic chromosomes is required for bipolarity of acentriolar female meiotic spindles by time-lapse imaging of mutants that lack cohesion between chromosomes. Both a spo-11 rec-8 coh-4 coh-3 quadruple mutant and a spo-11 rec-8 double mutant entered M phase with separated sister chromatids lacking any cohesion. However, the quadruple mutant formed an apolar spindle whereas the double mutant formed a bipolar spindle that segregated chromatids into two roughly equal masses. Residual non-cohesive COH-3/4-dependent cohesin on separated sister chromatids of the double mutant was sufficient to recruit haspin-dependent Aurora B kinase, which mediated bipolar spindle assembly in the apparent absence of chromosomal bipolarity. We hypothesized that cohesin-dependent Aurora B might activate or inhibit spindle assembly factors in a manner that would affect their localization on chromosomes and found that the chromosomal localization patterns of KLP-7 and CLS-2 correlated with Aurora B loading on chromosomes. These results demonstrate that cohesin is essential for spindle assembly and chromosome segregation independent of its role in sister chromatid cohesion.

  View details for DOI 10.1371/journal.pgen.1010136

  View details for Web of Science ID 000924663300001

  View details for PubMedID 36279281

  View details for PubMedCentralID PMC9632809

• Evidence for anaphase pulling forces during <i>C</i>. <i>elegans</i> meiosis JOURNAL OF CELL BIOLOGY Danlasky, B. M., Panzica, M. T., McNally, K. P., Vargas, E., Bailey, C., Li, W., Gong, T., Fishman, E. S., Jiang, X., McNally, F. J. 2020; 219 (12)

  Abstract

  Anaphase chromosome movement is thought to be mediated by pulling forces generated by end-on attachment of microtubules to the outer face of kinetochores. However, it has been suggested that during C. elegans female meiosis, anaphase is mediated by a kinetochore-independent pushing mechanism with microtubules only attached to the inner face of segregating chromosomes. We found that the kinetochore proteins KNL-1 and KNL-3 are required for preanaphase chromosome stretching, suggesting a role in pulling forces. In the absence of KNL-1,3, pairs of homologous chromosomes did not separate and did not move toward a spindle pole. Instead, each homolog pair moved together with the same spindle pole during anaphase B spindle elongation. Two masses of chromatin thus ended up at opposite spindle poles, giving the appearance of successful anaphase.

  View details for DOI 10.1083/jcb.202005179

  View details for Web of Science ID 000607622500005

  View details for PubMedID 33064834

  View details for PubMedCentralID PMC7577052