Biology Reference
In-Depth Information
In-R
Growth
factor
receptors
PI-3-K
PTEN
Akt
TSC1/2
Ras
S6k
myc
Expansion
Proliferation
FIGURE 22.12
The role of the insulin receptor signal transduction pathway in controlling expansion and
proliferation of cells. This diagram is based on Baron et al.
71
and Kronenberg.
72
studies in which mutants were generated only in defined areas of the embryo, to avoid
embryonic lethal phenotypes: only those parts of the embryos carrying the loss-of-function
cells show the phenotype). Conversely, over expression of the inhibitor of the pathway
PTEN results in small organs. This PTEN is the same molecule discussed in the context of
cell guidance in Chapter 9.
The conclusion from these observations is that interfering with the insulin pathway alters
cell size and removes an organ's ability to compensate for this. IGF signalling is therefore
probably the pathway that determines the 'set point' of tissue size that can be reached
through compensated regulation of cell size and number.
INTERPL
AY BETWEEN GLOBAL AND ORGAN-SPECIFIC
SIGNALS
The use of 'global' signals allows the body to coordinate the growth of all of the compon-
ents of complete systems. For example, hormones such as GH enable the coordination of the
growth rates of different bones in the skeleton. In development of animals such as humans,
this global coordination is important because there are distinct phases in long-bone growth.
Rates of elongation are very high in foetal life but then fall away rapidly until the age of about
three and fall away more slowly thereafter. At puberty, growth rates are again increased and
then fall away again until the growth plates cease to exist and further growth is impossible. It
is obviously important that different bones (for example in the left and right legs) switch
between different growth rates together.
The rate of growth in a growth plate is not set, however, purely by hormones derived from
the pituitary gland, etc., but rather by a combination of external signals and regulatory
