Developmental Control of the Cell Cycle: Insights from Caenorhabditis elegans

Abstract

During animal development, a single fertilized egg forms a complete organism with tens to trillions of cells that encompass a large variety of cell types. Cell cycle regulation is therefore at the center of development and needs to be carried out in close coordination with cell differentiation, migration, and death, as well as tissue formation, morphogenesis, and homeostasis. The timing and frequency of cell divisions are controlled by complex combinations of external and cell-intrinsic signals that vary throughout development. Insight into how such controls determine in vivo cell division patterns has come from studies in various genetic model systems. The nematode Caenorhabditis elegans has only about 1000 somatic cells and approximately twice as many germ cells in the adult hermaphrodite. Despite the relatively small number of cells, C. elegans has diverse tissues, including intestine, nerves, striated and smooth muscle, and skin. C. elegans is unique as a model organism for studies of the cell cycle because the somatic cell lineage is invariant. Somatic cells divide at set times during development to produce daughter cells that adopt reproducible developmental fates. Studies in C. elegans have allowed the identification of conserved cell cycle regulators and provided insights into how cell cycle regulation varies between tissues. In this review, we focus on the regulation of the cell cycle in the context of C. elegans development, with reference to other systems, with the goal of better understanding how cell cycle regulation is linked to animal development in general.

A two-step mechanism for the inactivation of microtubule organizing center function at the centrosome

“…FP treatment in pre-growth cells inhibited the accumulation of SPD-2 and SPD-5 at the centrosome and growth-stage FP treatment induced their precocious disassembly. Metaphase stage FP treatment had relatively little effect on SPD-2 and SPD-5 centrosomal localization, consistent with the fact that CDK is normally inactivated shortly after metaphase (Kipreos and van den Heuvel, 2019). SPD-2 and SPD-5 both accumulated at centrosomes following pre-growth OA treatment, albeit to a lesser extent than in control cells.…”

DNA replication and mitotic entry: A brake model for cell cycle progression

“…Thus far we have mainly focused on the intrinsic signaling circuits that determine cell cycle progression, but cell proliferation is highly sensitive to external cues. A multitude of developmental or experimental conditions can slow down or arrest the cell cycle (Edgar and Lehner, 1996;Elledge, 1996;Kipreos and van den Heuvel, 2019). As a result, the term "checkpoint" has gained a second meaning in cell biology, referring to a halt in cell cycle progression due to external stresses.…”

Molecular competition in G1 controls when cells simultaneously commit to terminally differentiate and exit the cell-cycle

“…when along the differentiation trajectory is the post-mitotic state established and how do cells coordinate cell cycle exit with the expression of regulators of terminal differentiation during this highly dynamic transition period? Even in C. elegans, where cell lineages are highly stereotyped, it is not well understood how developmental factors coordinate with the canonical cell cycle regulators to regulate differentiation (Kipreos and van den Heuvel, 2019). Since cell division and differentiation are often asynchronous processes with different timescales, it has been difficult to precisely define the order of events during the proliferation-differentiation decision and the relationship between cell division and differentiation.…”