Mechanical control of tissue growth in animal skin For some animal tissues, such as mammalian
skin, it is clear that the growth of the
skin is ultimately determined by the size of the body whose surface area the skin covers. This suggests that
cell proliferation in skin
stem cells within the
basal layer is likely to be mechanically controlled to ensure that the skin covers the surface of the entire body. Growth of the body causes mechanical stretching of the skin, which is sensed by skin
stem cells within the
basal layer and consequently leads to both an increased rate of
cell proliferation as well as promoting the planar
orientation of
stem cell divisions to produce new skin
stem cells, rather than only producing
differentiating supra-basal daughter cells.
Cell proliferation in skin
stem cells within the
basal layer can be driven by the mechanically-regulated
YAP/
TAZ family of
transcriptional co-activators, which bind to
TEAD-family DNA binding
transcription factors in the
nucleus to activate target
gene expression and thereby drive
cell proliferation. For other animal tissues, such as the bones of the
skeleton or the internal mammalian organs
intestine,
pancreas,
kidney or
brain, it remains unclear how developmental
gene regulatory networks encoded in the
genome lead to organs of such different sizes and proportions.
Hormonal control of tissue growth in the entire animal body Although different animal tissues grow at different rates and produce organs of very different proportions, the overall growth rate of the entire animal body can be modulated by circulating hormones of the
Insulin/
IGF-1 family, which activate the
PI3K/AKT/mTOR pathway in many cells of the body to increase the average rate of both
cell growth and
cell division, leading to increased
cell proliferation rates in many tissues. In mammals, production of
IGF-1 is induced by another circulating hormone called
Growth Hormone. Excessive production of
Growth Hormone or
IGF-1 is responsible for
giantism while insufficient production of these hormones is responsible for
dwarfism.
Developmental control of tissue growth during adult tissue homeostasis Adult animal tissues such as
skin or
intestine maintain their size but undergo constant turnover of cells by proliferation of
stem cells and
progenitor cells while undergoing an equivalent loss of differentiated daughter cells via sloughing off. Gradients of
Wnt signaling pathway activity appear to have a fundamental role in maintaining proliferation of stem and progenitor cells, at least in the intestine, and possibly also in skin.
Regenerative tissue growth after wounding or other types of damage Upon tissue damage, there is an
upregulation in the activity of many pathways that control tissue growth, including the
YAP/
TAZ pathway,
Wnt signaling pathway, and
growth factors that activate the
PI3K/AKT/mTOR pathway. == References ==