Cytokinesis is defined as the physical division of one cell into two and occurs at the end of the cell cycle. Gestation and development are defined by dividing cells; as an organism develops, cells must duplicate their genetic material, divide, and form two daughter cells. This process is fundamental to all life on our planet. Here, I present work that builds upon our understanding of cytokinesis, focusing on the differential requirements for cytokinesis in different cell types in the early C. elegans embryo, specifically, the P2 cell of the 4-cell embryo.
The textbook view of cytokinesis is that all animal cells divide using the same molecular machinery. Yet, growing evidence supports both cell type-specific regulation of cytokinesis and cell type-specific consequences for cytokinesis failure. The 4-cell C. elegans embryo is a powerful model for studying cell type-specific differences in cytokinesis as the cells are already programmed to form distinct cell linages, and previously, we identified cell type-specific regulation of cytokinesis at the 4-cell stage. We weakened the contractile ring using a temperature sensitive (ts) diaphanous formin/CYK-1 mutant. Under this condition, the two anterior cells (ABa and ABp) always failed in cytokinesis, whereas the two posterior cells (EMS and P2) divided successfully at a high frequency, even without detectable F-actin in the cell division plane.
Here we focus on the cell type-specific protection of cytokinesis in the P2 germ precursor cell, required to produce all gametes in the adult worm. Using a candidate-based RNAi mini-screen to identify genes required for protection of P2 cytokinesis in the formin(ts) embryos, we identified members of the CCCH Zn2+-finger protein family that are enriched in P2 and required for proper germ cell fate specification. Depletion of MEX-1, PIE-1, or POS-1 led to loss of cytokinetic protection and P2 cytokinesis failure in formin(ts) mutants, but not in control embryos. While depletion of MEX-1 affected multiple cell types, PIE-1 and POS-1 acted exclusively in the P2 cell.
Further analysis revealed these germ fate regulators protect cytokinesis by preventing excessive accumulation of septin/UNC-59 and its binding partner, anillin/ANI-1, on the cell cortex in the P2 cell division plane, both negative regulators of actomyosin constriction during cytokinesis in many contexts. We further found that co-depletion of septin and PIE-1 was sufficient to both reduce anillin levels at the P2 division plane and restore cytokinetic protection of P2 in formin(ts) mutant embryos. Thus, germ fate specification protects the P2 germ precursor cell from cytokinesis failure upon damage to the actin cytoskeleton at least in part by controlling the levels of septin and anillin at the division plane.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/kw4t-pp33 |
| Date | January 2024 |
| Creators | Connors, Caroline Quinn |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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