06-Determination and Differentiation
06-Determination and Differentiation
06-Determination and Differentiation
Determination and
Differentiation
Development
During development, a human or other
multicellular organism goes through an amazing
transformation, one at least as dramatic as the
metamorphosis of a caterpillar turning into a butterfly.
Over the course of hours, days, or months, the
organism turns from a single cell called
the zygote (the product of sperm meeting egg) into a
huge, organized collection of cells, tissues, and
organs.
Sources of information in development
Intrinsic (lineage)
information is inherited
from the mother cell, via
cell division. For instance,
a cell might inherit
molecules that "tell" it that
it belongs to the neural, or
nerve cell-producing,
lineage of the body.
Extrinsic (positional) information is received from the cell's
surroundings. For instance, a cell might get chemical signals from a
neighbor, instructing it to become a particular kind of photoreceptor
(light-detecting neuron).
Determination
Process whereby an embryonic cell or group of cells
becomes fixed into a predictable developmental pathway.
In other words, during the early stages of development,
cells commonly become “determined” or committed to a
particular cell type.
When a cell “chooses” a particular fate, it is said to be
determined, although it still "looks" just like its
undetermined neighbors. Determination implies a stable
change - the fate of determined cells does not change.
At first, cells may be specified, earmarked
for a certain fate but able to switch given the
right cues. Next, they may
become determined, meaning that they are
irreversibly committed to a certain fate. Once a
cell is determined, even if it’s moved to a new
environment, it will differentiate as the cell
type to which it's become committed.
cardiac muscle
striated muscle
adipocyte
squamous epithelium
cuboidal epithelium
bipolar neuron
multipolar neuron
other cell types
Differentiation
•Differentiation is the process in which cells
become specialized structurally and
functionally.
•When the embryo is small, each cell has the
potential to develop in many different ways.
•As development proceeds, the possibilities
available to individual cells narrow, until each
cell’s fate is determined and the cell has
differentiated.
Eventually, most cells in the body differentiate, or
take on a stable, final identity. Examples of differentiated
cell types in the human body include neurons, the cells
lining the intestine, and the macrophages that gobble up
bacterial invaders in the immune system.
Each differentiated cell type has a specific gene
expression pattern that it maintains stably. The genes
expressed in a cell type specify proteins and functional
RNAs needed by that particular cell type, giving it the
right structure and function to do its job.
For example, the diagram above shows two genes
that are differently expressed between a liver cell and a
neuron. One gene, encoding part of an enzyme that
breaks down alcohol and other toxins, is expressed only
in the liver cell (and not in the neuron). The other gene,
encoding a neurotransmitter, is expressed only in the
neuron (and not in the liver cell). Many other genes
would also be expressed differently between these two
cell types.
Differentiation results from
differential gene expression:
The specific components of a given cell
provides its special characteristics. These
components are either synthesized by proteins,
or are themselves proteins. By expressing
different subsets of genes, two cells contain
different subsets of gene products (proteins).
How can we observe
that cells from two
tissues express
different genes? There
are two blots: the
Southern blot shows
that tissues A and B
both contain a
particular gene.
However, the Northern
blots shows that only
tissue A contains RNA
transcribed from that
particular gene
Differential gene expression is not a
result of differential loss of the genetic
material, DNA, except in the case of the
immune system. That is, genetic information is
not lost as cells become determined and begin
to differentiate.
In fact, even the nuclei of adult cells contain ALL
of the information needed for the construction of an
entire organism, if provided with the proper cytoplasmic
components. The cloning of Dolly from an adult cell is a
major breakthrough, not only because of potential
biotechnological applications, but because of the
importance of this result for basic science: the result is
the most convincing evidence for the theory of
differential gene expression.
In order to clone Dolly, udder cells were removed
from a Finn Dorset ewe and starved for one week to
cause G0 arrest. Nuclei from arrested Finn Dorset udder
cells were fused with enucleated eggs from a Scottish
Blackface ewe, and then stimulated to re-enter the cell
cycle.
After a few rounds of cell division, the embryo was
transplanted into a surrogate Scottish Blackface mother.
The sheep that was born was genetically identical to the
Finn Dorset ewe, which was the source of the nucleus.