Cell Differentiation

Dr. Ritesh Vaidya

Senior Lecturer
Mehsana Urban bank Institute of
Biosciences
Ganpat University
Kherva-382 711

Introduction

It is known that the protoplasm of different

parts of the embryo is somewhat different. The
initial differences in the protoplasmic regions
may be supposed to affect the activity of
genes. The genes will then in turn affect the
protoplasm, which start a new series of
reciprocal reactions. In this way we can picture
to ourselves the gradual elaboration and
differentiation of the various regions of the
embryo.
-T. H. Morgan, 1934

Introduction

Cell differentiation is
the process by which
stable
differences
arises between cells.
All higher organisms
develop
from
a
single
cell,
the
fertilized
ovum,
which gives rise to
the various tissues
and organs.

Mature frog oocyte

Events of Cell Differentiation

In most
animal species females produce large
unfertilized eggs that contain most of the materials and
nutrients required to form an embryo. Development is
triggered by fertilization. The sperm contributes a small,
condensed nucleus (male pronucleus), which rapidly
enlarges in the egg cytoplasm, fuses with female
pronucleus, and finally divides.
The fertilized egg then undergoes a series of vary rapid
cyclesconsisting of DNA synthesis followed by cell
divisions.
These divisions are called cleavage, because, unlike
normal cell division, the cytolasm is partitioned without
growth.

Events of Cell Differentiation

Blastula- The cells form a

hollow sphere (blastula) in
which tissues are not yet
evident.
Gastrulation- Some of the
cells then invaginate in a
series of cell movement
known as gastrulation, and
the
first
sigs
of
morphological differentiation
appear.
These complex changes
take
place
in
a
comparatively short time.
Xenopus
laevis
a
swimming
tadpole
containing
most
differentiated tissues such
as blood, nerve, eye, muscle

Variable Gene Activity

Cell specialization involves the preferential
synthesis of some specific proteins such as
hemoglobin in erythrocytes, antibodies in
plasma cells and ovalbumin in oviduct.
Each eukaryotic cell expresses only a small
percentage of the genes it contains, and cells
of different tissues express different sets of
genes.
Necessary to understand the mechanisms of
gene regulation.

Whether all genes, present in a cell are tissue specific?

The housekeeping genes Expected to be active in all types
of cells.
Required for building membranes, ribosomes, mitochondria and
glycolytic enzymes, which are components common to all types
of cells.
Luxury functions The genes that are expressed
differentially, such as globin, ovalbumin and immunoglobulins.
Better knowledge of cytoplasmic functions is also important for
clarifying how the initial differences between cells are
established in early embryos.
Cytoplasmic determinants It is believed that the cytoplasm
of most eggs contains cytoplasmic determinants of
development which at some point become unequally distributed
among the cells of an embryo and subsequently change the

Characteristics of Cell Differentiation

The differentiated state is Stable Once the differentiated

state is established, it is very stable and can persist
throughout many cell generations.
e.g. Nerve Cells (Neuron), skin cell
These persistent changes are very different from the type of
regulation involved in enzyme induction and repression in
bacteria, which is specially designed to respond rapidly to
changes in the environment.
Cell differentiation is induced by various stimulus The
cell differentiation is induced in the organism by various
stimuli, but once it has been established, it can persist even in
the absence of the stimuli.

Determination can precede Morphological Differentiation

Before it is possible to recognize morphologically that a cell

has differentiated, there is a period during which the cell is
already committed to a particular change.
After this determination has been made, the cell will
differentiate along a specific pathway even if several cell
generations
intervene
before
overt
morphological
differentiation.
e.g. The imaginal discs of Drosophila
The discs are groups of cells that are present in the larva in
an undifferentiated form, but that upon metamorphosis will
give rise to legs, wings, antennae and so forth.
Disc transplantation experiment by Hadorn.

Cell Differentiation Results from stepwise

decisions that are genetically controlled.

Understanding the complicated patterns of cell arrangements can be

made simple by the use of genetics, which allows the analysis of the
effect of single gene o development.
T.H. Morgan discovered famous white-eyed fly.
Morgan realized that development could not be understood before
understanding how genes worked, and so he began studying genes
by obtaining and analyzing mutants.
The most interesting mutations are those that can, by inactivating a
single gene, change one segment of the body into a different one.
These are called homeotic mutations.

Adult flies have a head

(made of six segments),
three thorasic segments
(pro, meso and metathorax)
and
eight
abdominal
segments.
Each thorasic segments has
a pair of legs, and the
second thorasic segment
also has a pair f wings. The
third thorasic segment does
not have wings in flies but
instead a pair of halters,
which are small drumstickshaped stumps used for
equilibrium during flight.

A mutant four winged fly

generated by a mutation in
the so-called bithorax locus.
A single mutation changes a
haltere into a wing. The
bithorax locus is a complex of
many genes. Some of these
genes suppress the formation
of lags in the abdominal
segments, which suggests
that insects evolved from
ancestors such as milipedes
with a pair of legs in each
segment.
Another homeotic mutation
called
antennapedia

Localization of Cytoplasmic Determinants in

Eggs

Experimental Embryology 100 years Ago

O. Hertwig in 1875 showed that the sea urchin sperm

donated a nucleus , which later fused with the female one.
Thus it seemed that the nucleus would contain the hereditary
material.
Weissmann proposed his theory of heredity in the year 1883
and proposed that it is the germ cells that carry heredity and
that the body or soma is a mere offshoot of the germ cells
whose main function is to carry the germ cells.
Although Weissmanns views on heredity were essentially
correct, his theory on development turned out to be wrong. He
proposed that the fertilized egg had all the information to
make an individual, but that with each successive division part
of the information was lost.
Weissmann thought that in the end some cells retain only
genetic material to make a specific type of tissue, and
lose all other genetic material.

The Genome Remains Constant during Early DevelopmentNuclear Transplantation

Experimental embryology began in 1888 when Roux killed

one of the cells of the frog embryo at the two-cell stage with a
hot needle. He observed that the other cell gave rise to a halfembryo, usually a right or a left half.
In 1892 Driesch separated the two cells of a sea urchin
embryo and found that both could give rise to complete,
although smaller, embryos.
Roux experiment leaving the dead cell in situ interfered with
the invagination of cells during gastrulation.
J. B. Gurdon has carried out nuclear transplantation
experiments in the frog egg.
Xenopus laevis unfertilized eggs can be irradiated with
ultraviolet light to destroy the endogenous nuclei and can then
be injected with a single Xenopus diploid nucleus.

Cytoplasmic Localizations May Determine the Initial

Differences between Embryonic Cells

If the information contained in the cleavage nuclei is identical, then

the initial differences between cells should reside in the cytoplasm
they inherit.
In some eggs the segregation of cytoplasmic components, which are
thought to be able to affect the activity of genes, is particularly clear.
In Dentalium, the cytoplasm of the vegetal pole is extended
transiently during the first and second cleavage. This polar lobe
lacks a nucleus and after cell division is incorporated into one of the
blastomeres.
The cell that inherits the polar lobe cytoplasm eventually gives rise
to the mesoderm.
E. B. Wilson (1904) removed the polar lobe at the two-cell stage by
sucking the eggs up and down a thin pipette. He found that the
lobeless embryos lacked mouth, shell gland, and foot, as well
as other mesodermal tissues, and he concluded that the polar
lobe cytoplasm contains mesodermal determinants.

Germ Cell Determinants

Best example of determinants in development is provided by the

germ plasm.
Amphibians and other eggs contain in their vegetal pole a
specialized region of cytoplasm that can be recognized
morphologically by the presence of special granules.
Drosophila eggs have an equivalent region located in the posterior
pole of the egg which is therefore called the poleplasm. This
cytoplasm has the property of inducing germ cell formation i.e. those
cells that contain the germ plasm will eventually become the germ
cells of the new organisms.
When the posterior poles of eggs are irradiated with ultraviolet light,
sterile animals were obtained. If UV-treated eggs are injected with
pole-plasm of normal eggs, fertile flies are obtained.
If cytoplasm containing the germ cell determinants is injected into
the anterior part of a Drosophila egg, germ cells develop in an
anterior position.

Germ Cell Determinants

The germ cells are set apart early in development in a great many
organisms and the clearest example is the nematode Ascaris
megalocephala.
Boveri carried out extensive work and stated that the future germ cells can
be recognized because the chromosomes remain intact, while somatic cells
undergo a process called chromatin diminution.
Ascarias germs cells have only two large chromosomes, which have a
diffuse centromere.
In the cells that will become somatic, the central part of the
chromosomes breaks into multiple small chromosomes, and the ends
remain as visible chromatin masses in the cytoplasm of the daughter cells
from which they are eventually lost.
The germ lines does not undergo this chromatin diminution process.
At each cleavage division a single cell retains its chromosomes intact.
Thus, at fifth cleavage the embryo has 31 somatic cells and one germ cell.
Boveri reasoned that there must be a cytoplasmic substance that
becomes segregated into a single cell of the embryo and protects its
chromosomes from chromatin diminution.

Egg Stockpile Materials for Use During Early Development

Eggs are in general very large cells that stockpile many of the
molecules required for early development.
Xenopus egg contains about 1,00,000 times more RNA
polymerases, histones, mitochondria and ribosome than a
normal adult Xenopus somatic cell.
The reason for accumulating these ready-made materials
during oogenesis, rather than making them de novo
during early embryogenesis is the extraordinary rapid
rate of cell division during cleavage.
This rapid pace allows little time for new RNA and protein
synthesis, but it is during this period that the first differences
between cells are established.
Presumably most of the developmentally important
substances are made during oogenesis and stored in the egg.

The Mid-Blastula Transition

The first cleavage of the Xenopus egg takes place 90 minutes after
fertilization.
The 11 subsequent cleavages take place synchronously every 35
minutes. This compares with a doubling time of 24 hours for an adult
frog somatic cell.
In order to achieve this extraordinary short cell cycle, cleaving
embryos increase the number of origins of replication in their DNA
which shortens the S phase and omit the G1 and G2 phases of the
cell cycle, so that the end of DNA synthesis is immediately
followed by mitosis.
During this initial phase of development there is no transcription of the
DNA.
After 12th cleavage, or 4000-cell stage, the cell cycles become longer
and asynchronous, the cells become motile and RNA synthesis starts.
The turning point in development is called mid-blastula transition.
several types of RNA start to be expressed simultaneously at the midblastula transition.

The Mid-Blastula Transition

Why they are not expressed earlier?

There is a critical ratio of nuclei to egg cytoplasm before
transcription can start.
Polyspermic fertilization or the injection of large amounts
of extra DNA will induce the mid-blastula transition
earlier.
It seems that Xenopus eggs may have a substance that
binds to chromatin and turns it off transcriptionally.
The amount of this substance would be sufficient to
block up to 4000 nuclei, but then become exhausted and
expression of the genome would start.

Cell Interactions Become Increasingly Important as

Development Advances

Cytoplasmic determinants laid down in the egg during

oogenesis are undoubtedly very important in establishing
early differences between cells, they cannot entirely explain
development.
No evidence of cytoplasmic localization in mammalian eggs.
As the development advances, cell interactions become
increasingly important.
At gastrulation, extensive cell movements and migrations
occur, and different types of cells interact with each other in
the phenomenon known as embryonic induction.

Cell Interactions Become Increasingly Important as

Development Advances

The influence of neighbouring cells on cell differentiation can

sometimes be quite dramatic.
Tetratomas are tumors of the germ cells, which are the most
frequent tumors of human testis or ovary.
When they are proliferating rapidly, they remain
undifferentiated and are highly malignant, but sometimes they
have patches of several tissues, such as teeth, hair, muscle
and nerves.
In some ways tetratomas are like disorganized embryos.

Nucleocytoplasmic
Interactions

Introduction-Nucleocytoplasmic Interaction

Nucleus and cytoplasm are interdependent; one cannot survuve

without other.
The cytoplasm provides most of the energy for the cell through
oxidative phosphorylation and anaerobic glycolysis, and the
cytoplasmic ribosomes contain most of the machinery for
protein synthesis. The nucleus provides mRNA and also supplies
the other important RNA molecules.
Nucleus is necessary for cell survival- Waller (1852).
Nerve cells containing the nucleus survived, while the axons
degenerated.
In Protozoa, enucleated cells sustain most cellular activities.
However, these cells generally survive for only a limited
time and cannot multiply.
Example of extreme case of survival is Acetabularia.

Red Blood Cell Nuclei Can Be Reactivated by Cell Fusion

Cells can be fused through the use of inactivated Sendai

virus (a member of the parainfluenza viruses) and other
agents that affect membrane structure, such as
polyethyleneglycol and lysolecithin. Through this
techniques a nucleus can be placed in a different
cytoplasmic environment.
Heterokaryon- A single containing nuclei of two types.
Synkaryon- Both nuclei enter in mitosis synchronously,
divide and produce a hybrid cell line. The cells of a
hybrid cell line have a single nucleus containing
chromosomes from both parental nuclei.

Red Blood Cell Nuclei Can Be Reactivated by Cell Fusion

H. Harris (1965)- Chick erythrocyte nuclei are reactivated when

fused to He La cells.
These heterokaryones are of interest because the erythrocyte
nucleus does not normally synthesize RNA or DNA.
Chick erythrocytes are terminally differentiated cells that have a
highly condensed nucleus and are destined to die.
When fused to He La cells, the chick erythrocyte nucleus
increases 20 times in volume, disperse its chromatin, resumes
RNA synthesis, develops a nucleolus, and eventually replicates
its DNA.
The process is accompanied by the uptake of large amounts of
human nuclear proteins which are thought to reactivate the
erythrocyte nucleus.
These experiment clearly show that the synthesis of
macromolecules in a nucleus is controlled by the cytoplasmic
environment. Even though the erythrocytes are terminally
differentiated cells, they can resume RNA and DNA synthesis.

Red Blood Cell Nuclei Can Be Reactivated by Cell Fusion

Only the cell cytoplasm is required to reactivate the chick

erythrocyte nucleus. This was established by fusing erythrocytes to
enucleated He La cells, which were still able to reactivate the nuclei.
Populations of enucleated cultures cells can be obtained by
centrifugation after treatment with cytochalasin B, a drug that
inhibits actin microfilaments.
The detached nucleus in the pellet is surrounded by the cell
membrane and a small amount of cytoplasm and is called a
Karyoplast. The enucleated cytoplasm is called a cytoplast.
Cells enucleated by the cytochalasin method are viable for at least
two days after enucleation and perform many cell functions such as
cell movement, pinocytosis and contact inhibition.
Thus it is evident that many cytoplasmic functions are
independent of the cell nucleus.

Red Blood Cell Nuclei Can Be Reactivated by Cell

Fusion
Because karyoplasts are still surrounded by the cell
membrane, it is possible to fuse them to a different cytoplasm
by using Sendai virus.

Reconstituted cells, which arise from the fusion of a

karyoplast and a cytoplast can survive longer than the
enucleated cytoplasm, can synthesize RNA, and in some
cases can undergo cell division.
It is possible to activate latent genes coding for specific
proteins by fusion of differentiated cells.
Rat Hepatoma cells (Secrets albumin) fused with Mouse
lymphocytes (do not produce albumin).
Clones of this hybrid are able to produce both rat and mouse
albumin.

Cell Fusion Yields Pure Antibodies of Medical

Importance

When animals are injected with a macromolecule of a shape

that is recognized as foreign to that individual, antibodies
appear in the serum several days later.
Many different antibodies appear in the serum of an
immunized animal, each one recognizing a different part of
the antigens shape.
Furthermore, individuals of the same species have different
immunological responses, so that two antisera directed
against the same antigen can in fact be very different.
This is a major problem in medicine because, success or
failure of an organ transplantation depends on whether the
donor and the recipient patient have the correct
histocompatibility antigens on the cell surface.
Antibodies that can be used throughout the world as
standardized diagnostic reagents are highly desirable.

Cell Fusion Yields Pure Antibodies of Medical Importance

Antibodies are produced by the lymphocytes. Each antibodyproducing cell can synthesize only one type of antibody.
Lymphocytes do not multiply in culture, but G. kohler and C.
Milstein developed a technique whereby a single antibodyproducing cell can be propagated indefinitely in culture by
hybridization with a tumor cell.
Using Sendai virus, the lymphocytes from the spleen of the
mouse are fused to a mouse cell line derived from plasma cell
tumors.
The fusion with the tumor cell immortalizes the spleen
lymphocyte, which can be grown indefinitely in culture or
injected into the mice, where the cells produce secreting
tumors that can be maintained by serial transplantation.
Because all of the cells of one clone are derived from a single
lymphocyte, a monoclonal antibody of high purity is
produced.

Gene Expression by Somatic Nuclei Is Reprogrammed in Xenopus Oocytes

Frog oocytes are growing egg cells, obtained from the abdominal
cavity of frogs, which due to their large size (1.2 mm) and tolerance
for micromanipulation have been used in numerous microinjection
experiments.
Oocytes are active in RNA synthesis but do not synthesize DNA, ad
if somatic cell nuclei are injected into them, the transplanted nuclei
also show this type of synthetic activity.
The oocyte cytoplasm not only affects the pattern of
macromolecular synthesis but is also able to reprogram the
expression of individual genes in transplanted nuclei.
Nuclei of He La cells were injected into Xenopus oocyte.
The injected nuclei resemble the oocytes own nucleus
morphologically. The oocyte cytoplasm reprograms the gene
expression of the injected nuclei in such a way that only those genes
that are normally active in oocytes are expressed.

Gene Expression by Somatic Nuclei Is Reprogrammed in Xenopus Oocytes

In one such experiment, Xenopus cultured kidney cell

nuclei were injected into oocytes of a different amphibian
species the Salamander (Pleurodeles).
Those genes that are normally expressed in kidney cells
but not in oocytes became inactive after injection into
Pleurodeles oocytes.
More importantly, some oocyte-active genes that were not
expressed by the kidney cell nuclei were activated by the
oocyte cytoplasm.
The work with cell fusion and Xenopus oocytes
suggests that the cytoplasm of all cells contains
components that determine the state of activity of
nuclear genes. If these components were distributed
asymmetrically among daughter cells, they could play
a crucial role in the establishment of cell
differentiation.

Molecular Mechanisms of Cell

Differentiation

There is not a single eukaryotic gene for which we understand

for certain how it is expressed in some tissues and not in
others.
More we known about eukaryotic gene regulation, more it
becomes clear that eukaryotic genes are controlled at multiple
levels.
Two main mechanisms may be envisaged.
(1) Those in which genes are differentially activated at the
Transcriptional, Post-transcriptional or Translational level
or
(2) Those in which the genes themselves are altered by
Amplification, DNA rearrangements, and Methylation.
These mechanisms are known to operate in different cell
systems.

Control at the Level of Transcription

The nuclear transplantation experiments showed that in most cases

genes are not irreversibly lost during cell differentiation. Therefore
the differences between specialized cells must be explained in
terms of variable gene activity.
Transcriptional control is probably the most important mechanism
and the clearest example is provided by polytene chromosomes,
in which transcription can be directly visualized in the form of
puffs.
Transcriptional control has been clearly proven also for those genes
that code for abundant specialized proteins such as globin,
ovalbumin and silk fibrin.
To make hybridization probes for these genes the mRNA is copied
into DNA with reverse transcriptase (producing complementary DNA
or cDNA) and then the cDNA is cloned into plasmid.
With these hybridization probes, transcripts from the corresponding
gene can be detected only in those cells that produce the protein
product.

Control at the Level of Transcription

Enormous amounts of protein can be produced from the

transcriptional induction of a single protein-coding gene because
stable mRNA molecules can be translated many times.
A fully induced chicken ovalbumin gene makes 17 mRNA molecules
per minute (24,500 molecules a day).
A single silkworm fibroin gene makes 1010 protein molecules in the
course of a few days; roughly 105 times each.
Chromatin structure is one possible level at which transcription
may be controlled.
DNA methylation has also been considered a likely candidate to
control transcription. However, there are some species (e.g.
Drosophila) in which the DNA is never methylated, and the
significance of DNA methylation is still under debate.
The post transcriptional processing of the transcripts is also of
considerable regulatory importance.

Translational Control

One possibility that has been considered is that cells have

mechanisms by which some mRNAs can be translated in a given
cell type but not in others. Microinjection studies, however, have
shown that living cells can translate wide variety of mRNAs.
Microinjected Xenopus oocytes can translate SV 40 viral mRNAs.
In fact, the frog oocytes can also efficiently transcribe and process
injected DNAs, copying them into mature mRNAs, provided that
the DNA is injected into the nucleus, which contain RNA
polymerases and other factors required for transcription.
When the living oocytes are used solely as a test tube for translation
of mRNA, the mRNAs are introduced into the cytoplasm, which
contains the protein synthesis machinery.
Many mRNAs of animal and plant origin are efficiently translated in
oocytes such as those coding for globin, immunoglobulins,
thyroglobulin, interferon, collagen, tobacco mosaic virus coat
proteins and many others.
This finding suggests that oocytes do not have a mechanism that
excludes the translation of certain injected mRNAs.

Gene Amplification- A Rare Event

One way of obtaining differential gene activity would be to increase

the number of copies of a specific gene.
There are three circumstances in which gene amplification is known
to occur.
(1) Ribosomal DNA amplification observed in the oocytes of
amphibians and insects. Xenopus oocytes selectively replicate their
rDNA genes; a mature oocyte has 2 million copies of them
(compared to 900 for a diploid somatic nucleus) and 1000 nucleoli in
order to produce the vast number of ribodsomes (1012) contained in
a single egg.
(2) DNA replication observed in certain puffs of the dipterian
Rhynchosciara salivary gland polytene chromosomes. DNA
amplification can be visualized by an increase in the amount of DNA
in the particular polytene band when the puff collapses after the
phase of active RNA synthesis is over.
DNA puffs in Rhynchosciara code for salivary proteins.

(3) The third case is that of the egg shell (chorion) proteins of
Drosophila. The egg chorion is formed by the folicle cells during a
period of five hours. It has been found that the folicle cells replicate
more of a 90-kilobase segment of DNA containing the chorion
protein genes, so that finally it is 16 times more abundant than the
rest of the DNA.
Although it is clear that selective gene amplification does occur, in
all known cases the specially amplified DNA is not passed on to
future cell generations. The larval polytene salivary glands die at
metamorphosis, the follicle cells die when the egg is laid, and the
amplified oocyte rDNA is not inherited by the frog embryo.
Nucleic Acid Hybridization experiments have shown that there is
only one copy per haploid genome of globin or chicken ovalbumin
genes in all tissues, regardless of whether the gene is preferentially
expressed. In other words, a single globin gene, when fully
activated, can give rise to all the globin required by a red blood cell.
Gene amplification does not seem to be a widespread
phenomenon that can explain most cases of cell differentiation.

Drug Resistance Can Induce Gene Amplification

Cells in culture can be forces to amplify genes for certain

proteins by selective pressure.
Methotrexate is an analogue of folic acid that inhibits the
enzyme dihydrofolate reductase (DHFR).
The product of DHFR action (tetrahydrofolate) is required for
purine and thymidine biosynthesis.
Methotrexate is used for the clinical treatment of rapidly
dividing tumor cells and it has been known for a long time
that tumor cells eventually become resistant to the drug.
Although the amplification of genes can clearly be forced
by drugs or other selective agents, there is no evidence that it
plays a role in any developmental process leading to normal
cell differentiation.

Transposable Genes in Yeast and Trypanosomes

DNA rearrangements cause stable changes in patterns of gene

expression.
e.g. The mating-type switch in yeast.
Yeast generally propagates as haploid cells, but at a low frequency two
cells may fuse and produce diploids that are able to produce spores if
life becomes hard. The cells can fuse, however, only if they are of
opposite sex or mating type.
The mating type are a and .
When haploid strains of one mating type are cultured, some cells are
transformed into cells of the opposite sex with a certain frequency. If the
latter are cultured again, they can switch again. These changes are
stable and persist over several cell generations.
The genetic information for the or a mating types is stored in silent
places on yeast chromosomes. These storage sites are called silent
cassettes, and their expression is activated only when these genes are
transported into the expressed position on the MAT mating locus.
Another example of transposition of silent genes into an expression site
is provided by the surface antigens of Trypanosoma brucei.

Control of Immunoglobulin Secretion by Differential RNA

Processing

After a B lymphocyte has undergone DNA rearrangement, it expresses

IgM (and usually IgD as well) on its membrane.
This cell will stay quiescent until the binding of specific antigen to its
surface induces it to proliferate vigorously and to differentiate further.
Proliferation will produce clones of cells producing the same type of
antibody. The immune system works by the clonal selection (by
proliferation) of those B cells that have an antibody on their surface that
has a good fit with the shape of the antigen.
After a cell has been stimulated by antigen, it starts secreting IgM. This
switch from membrane-bound to secreted IgM is controlled at the
level of RNA processing.
After stimulation by antigen, the transcriptional unit is polyadenylated
earlier, eliminating the membrane exons and thus the hydrophobic
COOH region. The resulting IgM protein will now be secreted into the
surrounding medium.
Thus RNA processing is an important level of control in the
expression of immunoglobulin genes.

Cell Differentiation in Adult Tissues

Clearly gene expression can be regulated at many levels. We still do

not know why a globin gene (or any other gene) is active in red blood
cells and inactive in other cells.
It may turn out that the principles involved in the initial establishment of
the differentiated state will be very different from those involved in the
maintenance of differential gene expression.
In differentiation of adult tissues it is frequently observed that only
one of the daughter cells becomes specialized; the other one
remains as a stem cell, which is able to divide again.
During nerve cell differentiation in grasshoppers, some cell divisions
result in the formation of a neuron (ganglion cell) and a stem cell
(neuroblast), which are always in the same position and
morphologically recognizable. By introducing a needle at mitosis, it is
possible to rotate the spindle and chromosomes 180 degrees; but
despite this rotation, the resulting daughter cells still have the
neuron and stem cell in the normal position.
Thus, the ability to become a neuron does not depend on a
particular chromosome set but rather on the type of cytoplasm
inherited by the daughter cell.