Biology subjects

Labbe, J.-C.

Publications and source records attributed to Labbe, J.-C..

6 recordsLinked to original sources

bioRxiv2026

The flavin-containing monooxygenases OSGIN1 and OSGIN2 antagonize each other to favor cytokinesis completion

Cytokinesis is a fundamental process that bisects a mother cell into two distinct daughter cells via an ingressing ring of actomyosin. It initiates after anaphase chromosome separation by the mitotic spindle, which coordinates the activation of the small GTPase RhoA at the cell equator. We previously identified OSGIN1 as a flavin-containing monooxygenase enzyme required for cytokinesis completion via the regulation of RhoA activity. Here we show that the OSGIN1 paralog OSGIN2 is also a flavin-containing monooxygenase implicated in cytokinetic regulation. Cells lacking OSGIN2 have reduced RhoA activity and increased rates of cytokinesis failure, similar to OSGIN1-deleted cells. Strikingly, these phenotypes are suppressed in cells lacking both OSGIN1 and OSGIN2, indicating that the two proteins antagonize each other. Consistent with this, we find that OSGIN1 and OSGIN2 form both homo- and heteromeric complexes in vitro and in cells. Together, our results support a model in which OSGIN1 and OSGIN2 both function as negative regulators of RhoA signaling and that their heteromeric interaction during mitosis antagonizes their activity to favor cytokinesis completion.

cell biology↗

bioRxiv2026

Expanding the C. elegans toolkit with gonad explants

Animal development is a complex process that requires the coordination of a plethora of pathways in space and time. In several species, the availability of tissue explants has provided a simplified context that facilitates mechanistic investigations, particularly into dynamic events. Here, we demonstrate that extruded C. elegans gonads are a viable tissue explant system for this model organism. Using live-cell imaging, we show that C. elegans gonad explants retain many tissue properties that have been documented in vivo, including mitosis, meiosis, apoptosis and gametogenesis. We further show that C. elegans explants are acutely responsive to treatment by the microtubule depolymerizing drug nocodazole. Our work thus reveals C. elegans gonad explants as a new system in which live-cell imaging and acute drug treatment can be combined to decipher the mechanisms governing germline development.

developmental biology↗

bioRxiv2024

The spatiotemporal distribution of LIN-5/NuMA regulates spindle orientation and tissue organization in the C. elegans germ line

Mitotic spindle orientation sets the cell division plane and is thus critical for maintaining tissue organization. The C. elegans gonad is tube-shaped, with germ cells forming a circumferential monolayer around a shared inner core of cytoplasm called the rachis. Each germ cell is connected to the rachis via a stable cytoplasmic bridge, polarizing germ cells along their rachis-basal axis. How this tissue organization is maintained during development is unclear, as germ cells lack the canonical cell-cell junctions that, in other tissue types, ensure proper spindle orientation. Here we use live-cell imaging of C. elegans germ cells, both in situ and in gonad explants, to show that the microtubule force generator dynein and its conserved regulator LIN-5/NuMA regulate spindle orientation in C. elegans germ cells and are required for germline tissue organization. We uncover a cyclic, polarized pattern of LIN-5/NuMA cortical localization that predicts centriole/centrosome positioning throughout the cell cycle, providing a means to align spindle orientation with the tissue plane. This work reveals a new mechanism by which oriented cell division can be achieved to maintain tissue organization during animal development.

cell biology↗

bioRxiv2023

OSGN-1 is a conserved flavin-containing monooxygenase required to stabilize the intercellular bridge in late cytokinesis

Cytokinesis is the last step of cell division and is regulated by the small GTPase RhoA. RhoA activity is required for all steps of cytokinesis, including prior to abscission when daughter cells are ultimately physically separated. Like germ cells in all animals, the C. elegans embryonic germline founder cell initiates cytokinesis but does not complete abscission, leaving a stable intercellular bridge between the two daughter cells. Here we identify and characterize C. elegans OSGN-1 as a novel cytokinetic regulator that promotes RhoA activity during late cytokinesis. Sequence analyses and biochemical reconstitutions reveal that OSGN-1 is a flavin-containing monooxygenase. Genetic analyses indicate that the monooxygenase activity of OSGN-1 is required to maintain active RhoA at the end of cytokinesis in the germline founder cell and to stabilize the intercellular bridge. Deletion of OSGIN1 in human cells results in an increase in binucleation as a result of cytokinetic furrow regression, and this phenotype can be rescued by expressing a catalytically-active form of C. elegans OSGN-1, indicating that OSGN-1 and OSGIN1 are functional orthologs. We propose that OSGN-1 and OSGIN1 are novel, conserved monooxygenase enzymes required to maintain RhoA activity at the intercellular bridge during late cytokinesis and thus promote its stability, enabling proper abscission in human cells and bridge stabilization in C. elegans germ cells.

cell biology↗

bioRxiv2020

CentTracker: a trainable, machine learning-based tool for large-scale analyses of C. elegans germline stem cell mitosis

Investigating the complex interactions between stem cells and their native environment requires an efficient means to image them in situ. Caenorhabditis elegans germline stem cells (GSCs) are distinctly accessible for intravital imaging; however, long-term image acquisition and analysis of dividing GSCs can be technically challenging. Here we present a systematic investigation into the technical factors impacting GSC physiology during live imaging and provide an optimized method for monitoring GSC mitosis under minimally disruptive conditions. We describe CentTracker, an automated and generalizable image analysis tool that uses machine learning to pair mitotic centrosomes and which can extract a variety of mitotic parameters rapidly from large-scale datasets. We employ CentTracker to assess a range of mitotic features in GSCs and show that subpopulations with distinct mitotic profiles are unlikely to exist within the stem cell pool. We further find evidence for spatial clustering of GSC mitoses within the germline tissue and for biases in mitotic spindle orientation relative to the germlines distal-proximal axis, and thus the niche. The technical and analytical tools provided herein pave the way for large-scale screening studies of multiple mitotic processes in GSCs dividing in situ, in an intact tissue, in a living animal, under seemingly physiological conditions.

cell biology↗

bioRxiv2017

Anillin proteins stabilize the cytoplasmic bridge between the two primordial germ cells during C. elegans embryogenesis

Stable cytoplasmic bridges arise from failed cytokinesis, the last step of cell division, and are a key feature of syncytial architectures in the germ line of most metazoans. Whereas the C. elegans germ line is syncytial, its formation remains poorly understood. We studied the role of ANI-2, a noncanonical and shorter form of the actomyosin scaffold protein anillin that is expressed specifically during embryogenesis in the germ line precursor blastomere, P4. We found that the P4 blastomere does not complete abscission following cytokinesis, leaving a stable cytoplasmic bridge between the two daughter cells. Interestingly, depletion of ANI-2 results in a regression of the membrane partition between the two cells, indicating that ANI-2 is required to stabilize the cytoplasmic bridge. We identified several contractility regulators that, like ANI-2, localize to the cytoplasmic bridge and are required to stabilize it. Epistatic analysis of these regulators mutual dependencies revealed a pathway in which Rho regulators promote ANI-2 accumulation at the stable cytoplasmic bridge, which in turns promotes the accumulation of the non-muscle myosin II NMY-2 and the midbody component CYK-7 at the bridge, in part by limiting the accumulation of canonical anillin ANI-1. Our results uncover key steps in C. elegans germ line formation and define a set of conserved regulators that ensure the proper stability of the primordial germ cell cytoplasmic bridge during embryonic development.

cell biology↗