Size control mechanism in animals

Abstract

It remains to be mysterious for years as how distinct animals and their organs attain proper sizes. About a decade ago, Science listed “Top 125” to-be-solved scientific issues and included “size control mechanism” into it. Elucidation of the molecular, cellular and evolutionary mechanism of size control in animals especially in mammals would help us to better understand and manipulate the growth, development and regeneration of individuals and organs, which in turn will improve the modern regenerative medicine. Here in this review, we discussed the size control mechanism of animals and their organs. The animal body size is largely determined by their living environment, such as temperature, food and their geographic distribution. The animal’s organ size is directly associated with their body size and meanwhile affected by the organ function. Larger animals naturally have larger organ size and the organs which play more important physiological roles tend to have larger size. All organs finally evolve to a most “fit” size which reaches the balance between function and energy consumption. Basically body and organ size is determined by cell numbers but barely by cell size, so the size is tightly controlled by the rate and passages of cell proliferation. For a specific type of cells, how many progeny they produced is decided by how many cells are in need. Therefore, in the organ, the most abundant cells are those play most important physiological roles. As cell proliferation takes time, the lower animals with long life span can usually grow into very large size. And larger animals tend to have a longer fetal stage to accumulate sufficient immature stem cells to give rise to more mature cells. The cell proliferation rate is also inherently decided by the species or in another word their genetic background. Xeno-tranplantation of stem cell experiment demonstrated that the donor cells can form an organ whose size is in between the donor and recipient species, suggesting both genetic background and environment can affect the organ size. At molecular level, basically all regulator of cell proliferation can affect body and organ size. Some signal pathways such as mTOR and Hippo play critical roles in size control. Constitutive activation of Hippo pathway will generate over-size organs such as huge liver and gut. Other factors such as stem cell number, nutrition condition and mechanical pressure can also affect the organ and body size. To sum up, size matters for animals. The body and organ size is influenced by many factors of genetic, cellular and tissue levels. Animals of different size altogether form a biosphere with high complexity. They have diverse demand for sunlight, atmosphere, nutrition, space and trace elements, which makes them a stable ecological cycle.