What programs the size of animal cells?

Abstract

The human body is programmed with definite quantities, magnitudes, and proportions. At the microscopic level, such definite sizes manifest in individual cells - different cell types are characterized by distinct cell sizes whereas cells of the same type are highly uniform in size. How do cells in a population maintain uniformity in cell size, and how are changes in target size programmed? A convergence of recent and historical studies suggest - just as a thermostat maintains room temperature - the size of proliferating animal cells is similarly maintained by homeostatic mechanisms. In this review, we first summarize old and new literature on the existence of cell size checkpoints, then discuss additional advances in the study of size homeostasis that involve feedback regulation of cellular growth rate. We further discuss recent progress on the molecules that underlie cell size checkpoints and mechanisms that specify target size setpoints. Lastly, we discuss a less-well explored teleological question: why does cell size matter and what is the functional importance of cell size control?

Systemic orchestration of cell size throughout the body: influence of sex and rapamycin exposure in Drosophila melanogaster

“…Research is only just beginning to understand how cells sense and regulate their size, with studies focusing on cell-cycle checkpoints and molecular pathways involved in cell-autonomous and systemic control of cell size [ 33 , 43 ]. On a macroevolutionary timescale, the evolution of cell-cycle control appears to have involved the gradual incorporation of new signalling pathways into the conserved backbone formed by AMP-activated protein kinase (AMPK) and target of rapamycin (TOR), two protein kinases that act as signalling hubs to integrate and exchange information with the entire network of regulatory pathways [ 44 , 45 ].…”

Systemic orchestration of cell size throughout the body: Influence of sex and rapamycin exposure inDrosophila melanogaster

“…This is not a trivial question, especially as cell properties such as cell number, cell size, cell shape and organelle content should correspond closely to tissue-specific functions. The theory of optimal cell size (TOCS) [21,25,31,33,38,41,67,68] predicts that the cellular composition of an organism is optimized to selection pressures . CC-BY 4.0 International license perpetuity.…”

“…This is not a trivial question, especially as cell properties such as cell number, cell size, cell shape and organelle content should correspond closely to tissue-specific functions. The theory of optimal cell size (TOCS) [21,25,31,33,38,41,67,68] predicts that the cellular composition of an organism is optimized to selection pressures 8 through a compromise between the cost of plasma-membrane maintenance and the cell capacity to perform physiological functions. The relatively large area of the plasma membrane of small cells should increase the rates of oxygen and nutrient fluxes but incurs costs imposed by ionic gradients and the need to maintain adequate membrane structure.…”

“…There is also direct evidence that changes in cell size are a component of plasticity-and evolutionary-related changes in adult size [7,19,21,[25][26][27][28]. Undoubtedly, the number and size of the cells that make up an organism have consequences for organismal performance [29][30][31][32][33], but it is unclear whether the cellular structure of tissues is systemically organized throughout the metazoan body or whether it is arranged locally to suit tissue-specific functions. A clear answer to this fundamental question is unavailable largely because previous studies have rarely focused on cell-size variance among organisms and even then have tended to target single cell types [10,21,[34][35][36][37].…”

“…Research is only just beginning to understand how cells sense and regulate their size, with studies focusing on cell-cycle checkpoints and molecular pathways involved in cell-autonomous and systemic control of cell size [33,43]. On a macroevolutionary time scale, the evolution of cell-cycle control appears to have involved the gradual incorporation of new signalling pathways into the conserved backbone formed by AMP-activated protein kinase (AMPK) and target of rapamycin (TOR), two protein kinases that act as signalling hubs to integrate and exchange information with the entire network of regulatory pathways [44,45].…”