Epigenetic Control of Animal Development - Building the Most Complex Structure on Earth - page 127

changes in patterns of gene expression during the development of an individual.
From the viewpoint of genetics and the genetic program, it is paradoxical that from a
single cell with a single genotype, many different cell phenotypes arise during devel-
opment. If the zygote (the egg in parthenogenetic organisms) has a genetic program,
as many believe it does, differentiation in a higher-vertebrate organism of hundreds
of cell types, which differ from each other widely both in function and morphology,
would suggest that the embryo has to develop 100 different genetic programs—one
for each cell type.
Some biologists are still reluctant or hesitant to acknowledge that cell differentia-
tion is determined by other than genetic mechanisms. This sounds weird when one
remembers that more than 70 years ago, in 1941, Sewall Wright (1889-1988), the
great American geneticist and one of the founders of population genetics, admitted,
“The usual and most probable view is that cellular differentiation is cytoplasmic and
must therefore persist and be transmitted to daughter cells by cytoplasmic heredity”
( Wright, 1941 ).
Epigenetic Modes of Cell Differentiation
The first mode of cell differentiation observed during development is determined by
the asymmetric distribution of cytoplasmic factors (epigenetic information) in the
zygote. Even when the cleavage divisions are equal, cells resulting from the division
of the parental cell will have different fates, and these fates, obviously, are epige-
netically determined by the differential distribution of parental factors in the zygotic
cytoplasm.
During animal development, cell differentiation is often induced by extracellular sig-
nals, which determine their transformation into different cell types. For example, Wnt
and sonic hedgehog (Shh) signals from the neural tube in somites lead to the expres-
sion of skeletal muscle genes and differentiation of muscle cells ( Schmidt et al., 2000 );
signals from the brain and spinal cord, primarily vascular endothelial growth factors
(VEGFs), induce the formation of angioblasts in somites ( Hogan et al., 2004 ), etc.
Another mechanism of cell differentiation is asymmetric division of cells.
Asymmetric division of cells results in differential allocation of the cytoplasm in
daughter cells, leading to the emergence of different phenotypes in cells of the same
genotype. The mechanism of the asymmetric division that leads to cell differentia-
tion is an epigenetic mechanism ultimately based on the properties or behavior of
centrioles (microtubule organizing centers, more generally), which organize spin-
dle poles. In many species, the asymmetric divisions that determine cell fates start
since the early cleavage divisions. Neither genes nor chromosomes (nor DNA in
general) is involved in the asymmetric division of cells. This seems to be an exclu-
sive function of the cytoskeleton, microtubules, and actin filaments. One mechanism
is based on differences in the pushing/pulling forces of microtubules of the spindle
( Kaltschmidt and Brand, 2002 ) ( Figure 3.7 ).
The unequal cell division in the Drosophila neural larval stem cells results from
the furrow forming closer to one of the spindle poles. The two centrosomes resulting
from centrosome duplication migrate to the apical cortex, where they form a single