Bowerman B (2004) Nature "Cell division: timing the machine."

Bowerman B

[Nature, 2004]

During cell division everything must happen at the right time, or errors occur. A common cellular control device, protein phosphorylation, is now shown to time the assembly of a key part of the division machinery.

Bowerman B (2001) Cell Struct Funct "Cytokinesis in the C. elegans embryo: regulating contractile forces and a late role for the central spindle."

Bowerman B

[Cell Struct Funct, 2001]

Genetic and molecular studies in the nematode Caenorhabditis elegans have identified multiple essential pathways that regulate and execute cytokinesis in early embryonic cells. These pathways influence both the microfilament cytoskeleton and the microtubule cytoskeleton. Microfilaments are enriched throughout the cell cortex at all times during the cell cycle in embryonic cells. Cortical microfilaments are required for multiple processes in embryonic cells, including polar body extrusion during meiosis, anterior-posterior axis specification by the sperm-donated microtubule-organizing center, and cytokinesis during mitosis. In addition to contractile apparatus proteins that are required positively for cleavage furrow ingression, the Nedd8 ubiquitin-like protein modification pathway negatively regulates contractile forces outside the cleavage furrow during cytokinesis. Another pathway that acts positively during cytokinesis involves the mitotic spindle. The central spindle, where anti-parallel non-kinetochore microtubules overlap and are cross-linked, is required for a late step in cytokinesis, and other pathway(s) involved in membrane addition during cytokinesis may also require the central spindle. The amenability of C. elegans to classical genetics, the ease of reducing gene function with RNA interference, the completion of the genome sequence, and the availability of transgenic GFP fusion proteins that render the cytoskeleton fluorescent, all serve to make the early worm embryo an especially promising system for further advances in the identification of cytokinesis pathways, and in defining their interactions.

Bowerman B et al. (2006) Development "Degrade to create: developmental requirements for ubiquitin-mediated proteolysis during early C. elegans embryogenesis."

Bowerman B, Kurz T

[Development, 2006]

The ubiquitin protein conjugation system tags proteins with the small polypeptide ubiquitin. Most poly-ubiquitinated proteins are recognized and degraded by the proteasome, a large multi-subunit protease. Ubiquitin-dependent protein degradation is used as a regulatory tool for many essential processes, the best studied of which is eukaryotic cell cycle progression. More recently, genetic studies in C. elegans have identified multiple roles for the ubiquitin system in early development, where ubiquitin-dependent protein degradation governs such diverse events as passage through meiosis, cytoskeletal regulation and cell fate determination.

Schneider SQ et al. (2003) Annu Rev Genet "Cell polarity and the cytoskeleton in the Caenorhabditis elegans zygote."

Bowerman B, Schneider SQ

[Annu Rev Genet, 2003]

The anterior-posterior axis of the Caenorhabditis elegans zygote forms shortly after fertilization when the sperm pronucleus and its associated centrosomal asters provide a cue that establishes the anterior-posterior (AP) body axis. In response to this cue, the microfilament cytoskeleton polarizes the distribution of a group of widely conserved, cortically localized regulators called the PAR proteins, which are required for the first mitotic division to be asymmetric. These asymmetries include a posterior displacement of the first mitotic spindle and the differential segregation of cell-fate determinants to the anterior and posterior daughters produced by the first cleavage of the zygote. Here we review recent advances in our understanding of the mechanisms that polarize the one-cell zygote to generate an AP axis of asymmetry.

Munro E et al. (2009) Cold Spring Harb Perspect Biol "Cellular symmetry breaking during Caenorhabditis elegans development."

Munro E, Bowerman B

[Cold Spring Harb Perspect Biol, 2009]

The nematode worm Caenorhabditis elegans has produced a wellspring of insights into mechanisms that govern cellular symmetry breaking during animal development. Here we focus on two highly conserved systems that underlie many of the key symmetry-breaking events that occur during embryonic and larval development in the worm. One involves the interplay between Par proteins, Rho GTPases, and the actomyosin cytoskeleton and mediates asymmetric cell divisions that establish the germline. The other uses elements of the Wnt signaling pathway and a highly reiterative mechanism that distinguishes anterior from posterior daughter cell fates. Much of what we know about these systems comes from intensive study of a few key events-Par/Rho/actomyosin-mediated polarization of the zygote in response to a sperm-derived cue and the Wnt-mediated induction of endoderm at the four-cell stage. However, a growing body of work is revealing how C. elegans exploits elements/variants of these systems to accomplish a diversity of symmetry-breaking tasks throughout embryonic and larval development.

Pintard L et al. (2019) Genetics "Mitotic Cell Division in Caenorhabditis elegans."

Pintard L, Bowerman B

[Genetics, 2019]

Mitotic cell divisions increase cell number while faithfully distributing the replicated genome at each division. The <i>Caenorhabditis elegans</i> embryo is a powerful model for eukaryotic cell division. Nearly all of the genes that regulate cell division in <i>C. elegans</i> are conserved across metazoan species, including humans. The <i>C. elegans</i> pathways tend to be streamlined, facilitating dissection of the more redundant human pathways. Here, we summarize the virtues of <i>C. elegans</i> as a model system and review our current understanding of centriole duplication, the acquisition of pericentriolar material by centrioles to form centrosomes, the assembly of kinetochores and the mitotic spindle, chromosome segregation, and cytokinesis.

Gomes JE et al. (2002) Curr Biol "Caenorhabditis elegans par genes."

Gomes JE, Bowerman B

[Curr Biol, 2002]

Six par genes (par-1 through par-6) have been identified in Caenorhabditis elegans. Loss-of-function mutations in any par locus results in loss of anterior-posterior (AP) asymmetries during the first two embryonic cell divisions. This results in a failure to restrict developmental regulators to specific embryonic cells, mitotic spindle orientation defects and abnormal cell fate pattering. In sum, the par genes appear responsible for establishing asymmetries that define the AP body axis in C. elegans.

Nash B et al. (2004) Nature Cell Biology "Uncoiling centriole duplication."

Nash B, Bowerman B

[Nature Cell Biology, 2004]

The invariant duplication of the centriole once per cell cycle is critical for cell division. SAS-5 is the most recent of three coiled-coil centriolar proteins found to be required for centriole duplication in Caenorhabditis elegans.

Severson AF et al. (2002) Dev Cell "Cytokinesis: Closing in on the central spindle."

Severson AF, Bowerman B

[Dev Cell, 2002]

The central spindle is important for the completion of cytokinesis. Genetic and biochemical approaches have identified a tetrameric complex, made up of a mitotic kinesin-like protein and a Rho-GTPase activating protein, that mediates central spindle assembly.

Lyczak R et al. (2002) Dev Cell "Heads or tails: cell polarity and axis formation in the early Caenorhabditis elegans embryo."

Lyczak R, Bowerman B, Gomes JE

[Dev Cell, 2002]

In C. elegans, the first embryonic axis is established shortly after fertilization and requires both the microtubule and microfilament cytoskeleton. Cues from sperm-donated centrosomes result in a cascade of events that polarize the distribution of widely conserved PAR proteins at the cell cortex. The PAR proteins in turn polarize the cytoplasm and position mitotic spindles. Lessons learned from C. elegans should improve our understanding of how cells become polarized and divide asymmetrically during development.