Emerging roles of metazoan cell cycle regulators as coordinators of the cell cycle and differentiation

Abstract

In multicellular organisms, cell proliferation must be tightly coordinated with other developmental processes to form functional tissues and organs. Despite significant advances in our understanding of how the cell cycle is controlled by conserved cell‐cycle regulators (CCRs), how the cell cycle is coordinated with cell differentiation in metazoan organisms and how CCRs contribute to this process remain poorly understood. Here, we review the emerging roles of metazoan CCRs as intracellular proliferation‐differentiation coordinators in multicellular organisms. We illustrate how major CCRs regulate cellular events that are required for cell fate acquisition and subsequent differentiation. To this end, CCRs employ diverse mechanisms, some of which are separable from those underpinning the conventional cell‐cycle‐regulatory functions of CCRs. By controlling cell‐type‐specific specification/differentiation processes alongside the progression of the cell cycle, CCRs enable spatiotemporal coupling between differentiation and cell proliferation in various developmental contexts in vivo. We discuss the significance and implications of this underappreciated role of metazoan CCRs for development, disease and evolution.

Spatial organization and dynamics of chromosomes and microtubules during barley mitosis

“…During the cell cycle, the cells duplicate the majority of cellular components, genetic material, organelles, and other macromolecules, which are equally distributed into the newly emerging daughter cells (Gutierrez, 2009). The mitotic cell division and its regulation are studied in great detail in several fungal and metazoan models, including humans (Kimata et al., 2020; Kraikivski et al., 2015; Levine & Holland, 2018; Pintard & Bowerman, 2019). However, the amount of information about the kinetics and molecular control of mitotic division in plants is still limited.…”

Wnt signaling couples G2 phase control with differentiation during hematopoiesis

“…However, within a developing tissue, the cell cycle is also tightly controlled by the spatial and temporal context of the cell. Individual cells divide and differentiate at their own unique rates, and it is expected that extracellular signals will coordinate the timing and frequency of entry into, and exit from, the mitotic cycle 4,5 . For example, external signals perceived in G1 typically dictate whether a cell should self-renew, differentiate, or remain quiescent [6][7][8][9] .…”

Cytoskeletal Control and Wnt Signaling—APC’s Dual Contributions in Stem Cell Division and Colorectal Cancer

“…Spindle orientation responds to multiple layers of regulation that integrate cytoskeletal elements and cell cycle controls, including the role of cyclin-dependent kinases (CDKs), CDK inhibitors (CKIs), mitotic kinases, phosphatases and ubiquitin ligases (reviewed in [23,24]). In addition to those controls, extrinsic or intrinsic polarity cues determine the correct alignment of the mitotic spindle with respect to an axis of cell polarity.…”