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Chapter 21
THE GENETIC BASIS OF DEVELOPMENT
HOW A COMPLEX MULTICELLULAR ORGANISM DEVELOPS FROM A SINGLE
CELL?
In recent years scientists have applied the concepts and tools of molecular genetics to the study
of developmental biology.
Organisms chosen for study are called model organisms.

Fruit fly Drosophila melanogaster, the nematode Caenorhabditis elegans, the mouse
Mus musculus, the zebrafish Danio rerio, and the plant Arabidopsis thaliana.
EMBRYONIC DEVELOPMENT
Embryonic development involves cell division, cell differentiation, and morphogenesis.
During embryonic development, cells increase in number.
Cells also become specialized in structure and function. This is called differentiation.
As cells differentiate, they become arranged in tissues and organs. The physical processes that
give an organism its shape constitute morphogenesis.
The processes of cell division, differentiation and morphogenesis overlap in time.
Different types of cells in an organism have the same DNA.
The development of animals and plants differ in two major ways:

In animals, but not in plants, movements of cells and tissues are necessary to transform
the early embryo into the characteristic three-dimensional form of the organism.

In plants, but not in animals, morphogenesis and growth in overall size are not limited to
embryonic and juvenile periods but occur throughout the life of the plant.
Apical meristems are the tissues responsible for a plant’s continual growth and formation of
new organs.
Different cell types result from differential gene expression in cells with the same DNA.
Many experiments support the conclusion that nearly all the cells of an organism have genomic
equivalence: they all have the same genes.
In plants, at least, mature cells can dedifferentiate and then give rise to all the specialized cell
types of the mature organism. Any cell with this potential is said to be totipotent.
To use one or more somatic cells from a multicellular organism to make another genetically
identical individual is called cloning, and each new individual made in this way is called a clone.
Cloning of animals has been done by transplanting the nucleus of undifferentiated and
differentiated cells into unfertilized eggs of the same species without nucleus.
THE STEM CELLS IN ANIMALS
Stem cells are cells with two important properties:
1. They are relatively unspecialized cells and they continually reproduce themselves.
2. Under appropriate conditions, they differentiate into specialized cells of one or more
types.
The adult body has various kinds of stem cells, which serve to replace nonreproducing
specialized cells as needed.
1. Stem cells in the bone marrow give rise to all the different kinds of blood cells.
2. Stem cells in the adult brain continue to produce certain kinds of nerve cells.
Cells that can give rise to multiple cells types are called multipotent or pluripotent.

Pluripotent cells cannot give rise to whole individuals; they produced only a variety of cell
types. They are not totipotent.
Stem cells are being isolated and grown in culture. These cells are “immortal”; the reproduce
indefinitely using telomerases to maintain their telomeres in the chromosomes.
Scientist have been able to make cultured stem cells derived from several sources differentiate
into a wider range of specialized cell types than they normally due in the animal.
GENETIC AND CELLULAR MECHANIMS OF PATTERN FORMATION
Pattern formation in animals begins in the early embryo, when the animal’s basic body plan – its
overall three-dimensional arrangement - is established.
The earliest changes that set a cell on a path to specialization are subtle ones, showing up only
at the molecular level.
Determination refers to the events that lead to the observable differentiation of a cell.

At the end of determination, the cell is irreversibly committed to its final fate, and it is
said to be determined.

Observable cell differentiation is marked by the expression of genes for tissue-specific
proteins. Differentiated cells are specialists at making these tissue-specific proteins.
o
Liver cells make albumins; lens cells make crystallins, muscle cells make actin
and myosin.

These proteins are found only in a specific cells type and give the cells its characteristic
structure and function.

The appearance of mRNA for these proteins is the first evidence of differentiation.
TRANSCRIPTIONAL REGULATION
Transcriptional regulation is directed by maternal molecules in the cytoplasm and signals from
other cells.
In differentiation, two sources of information “tell” a cell which genes to express at any given
time.
1. The cytoplasm of the unfertilized egg contains mRNA and proteins encoded by the
mother’s DNA.
o
The cytoplasm of the egg is not homogeneous. Messenger RNA, proteins and
other substances and organelles are unevenly distributed in the unfertilized egg.
o
The maternal substances in the egg that influence the course of early
development are called cytoplasmic determinants. They regulate the
expression of genes that affect the developmental fate of the cells.
2. The environment around a cell is the other important source of developmental
information.
o
Chemical signals are sent from cells in the vicinity. These signal are encoded by
the embryos own genes. These signal molecules cause changes in the nearby
target cells, a process called induction.
o
Induction may be accomplished by the diffusion of chemical signals or by cell
surface interactions if the cells are in contact.
PATTERN FORMATION
Before morphogenesis can shape an animal or plant, the organism’s body plan — its overall
three dimensional arrangement — must be established.
Pattern formation is the development of a spatial organization in which the tissues and organs
of an organism are all in their characteristic places.
The axes of an animal are established very early: head and tail, right and left, front and back.
The molecular cues that control pattern formation, collectively called positional information,
tell a cell its location relative to the body axes and to neighboring cells and determine how the
cell and its progeny will respond to future molecular signals.
Cytoplasmic determinants are the substances that initially establish the axes of the animal
body’s.
GENETIC STUDIES ON DROSOPHILA
Key developmental events in the life cycle of Drosophila on page 422.
Genetic analysis of Drosophila reveals how genes control development.
Cytoplasmic determinants are already present in the unfertilized egg and are coded by genes of
the mother called maternal effect genes.

Mutations in these maternal effect genes result in defective phenotypes in the offspring
or the fertilized egg fails to develop properly.

Maternal effects genes are also called egg-polarity genes.
Messenger RNA produced by the mother and concentrated at one end of the egg act as pattern
setter for the anterior—posterior end of the embryo (bicoid gene, bcd); another group of
maternal effect genes establishes the dorsal-ventral axis.

An embryo whose mother has mutant bcd gene lacks the front half of its body and has
posterior structures at both ends.

The bcd mRNA is concentrated at the anterior end of the mature egg. After fertilization,
the mRNA is translated into protein. The bicoid protein diffuses from the anterior end
toward the posterior, resulting in a gradient of protein within the early embryo.

The bcd is a maternal morphogen, a substance that establishes the embryo’s axes.

Morphogens are the products of egg-polarity genes. They are transcription factors,
proteins that regulate the activity (transcription) of some of the embryo’s own genes.
Segmentation pattern
Gradients of these morphogens bring about regional differences in the expression of
segmentation genes, the genes of the embryo that direct the actual formation of segments
after the embryo’s major axes are defined.
A cascade of gene activations sets up the segmentation pattern in Drosophila.
There are three sets of segmentation genes. These sets of genes are activated sequentially and
provide the positional information for increasingly fine details of the animal’ body plan.
They produce transcription factors that directly activate the next set of genes in the hierarchical
scheme of pattern formation.
1. Gap genes map out the basic subdivisions along the anterior-posterior axis of the
embryo.
Mutations in the map genes cause an embryo to miss a given segment.
2. Pair-rule genes are the second set of segmentation genes to act. They subdivide these
broad bands into pairs of segments.
Mutations in the pair-rule genes causes to have half the normal number of segments
because every other segment fails to develop.
3. The segment polarity genes set the anterior-posterior axis of each segment.
Mutations in the segment polarity genes cause each segment to have a mirror image
repetition of one side on the other side.
Genes in each set not only activate the next set of genes but also maintain their own expression
in most cases.
Other segmentation genes operate indirectly, supporting the functioning of the transcription
factors in various ways, e.g. components of cell-signaling pathways, signal molecules and
receptor molecules.
The ultimate difference between cells is transcriptional regulation; the turning on and off of
certain genes.
Identity of body parts
Antennae, legs and wings develop on the appropriate segments. The anatomical identity of the
segments is set by master regulatory genes called homeotic genes.
Homeotic genes specify what kind of appendages and other structures are going to develop in
each segment.
Mutations of the homeotic genes causes the development of appendages on the wrong
segments, e. g. legs on the head.
All these genes encode transcription factors.
These regulatory proteins control the expression of the genes responsible for specific
anatomical structures.
Homeotic proteins activate genes specifying the proteins that actually build the fly structures.
The homeotic genes of Drosophila directly correspond to similar gene complexes in animals, all
the way up to man.
Many of the proteins found on fly pattern formation have been found to have close counterparts
throughout the animal kingdom.
“The homeotic genes (here called "HOM" genes) in Drosophila are clustered close to each other in the DNA, and they
set a ground plan for embryonic development in the fly. Vertebrates also contain homeotic (HOX) genes. Here, we
find four clusters, or complexes, of homeotic genes. These genes are closely related to the insect genes, their order
in the DNA is the same, and their action during embryonal development follows the same order in time and space in
the fly. Thus, the effects on the embryonic head-to-tail axis of these HOX genes largely follow the principles which
Lewis' set up for the fly.
It is actually possible to transfer a HOX gene from man to the embryo of a fruit fly, where it is can perform some of the
functions that the corresponding Drosophila gene normally executes. The location of our shoulders and hips on the
vertebral column, for example, may be controlled by specific homeotic genes.”
Source: http://nobelprize.org/medicine/laureates/1995/illpres/more-l-simgenes.html
http://nobelprize.org/medicine/laureates/1995/illpres/index.html
Induction
Induction is the signaling from one group of cells to another that brings about differentiation.

In the developing embryo, sequential inductions drive the formation of organs.
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The effect of an inducer can depend on its concentration.
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Inducers produce their effects via signal transduction pathways similar to those
operating in adult cells.
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The induced cell response is often the activation of genes (transcriptional regulation)
which in turn establishes the pattern of gene activity characteristic of a particular kind of
differentiated cell.
Apoptosis is programmed cell death.
Apoptosis is essential to the normal development of animals, e. g. normal development of the
nervous system; normal operation of the immune system; normal morphogenesis of the hand
and feet.
EVOLUTIONARY DEVELOPMENTAL BIOLOGY
There is a widespread conservation of developmental genes among animals.
Evolutionary developmental biologists compare developmental processes of different
multicellular organisms: evolutionary developmental biology = evo-devo

Their aim is to understand how developmental processes have evolved and how
changes in these processes can modify existing organismal features or lead to new
ones.
Homeobox genes
Homeotic genes in Drosophila include a 180-nucleotide sequence called the homeobox, which
specifies a 60-amino-acid homeodomain.
An identical or similar sequence of nucleotides has been discovered in genes of many other
animals including insects, nematodes, fish frogs, mammal and others.
Homologous homeotic genes of vertebrates and fruit flies have conserved the same
chromosomal arrangement.
Homeobox containing genes are often called Hox genes, especially in mammals.
From these similarities in the homeotic genes of different unrelated organisms, we can deduce
that the homeobox DNA sequence evolved very early in the history of life and that it is
sufficiently valuable to organisms to have been conserved in animals virtually unchanged for
hundreds of millions of years.
A homeodomain is a polypeptide segment of a protein that binds to DNA when the protein
functions as a regulator, a transcription factor.

The homeodomain consists of three α helices, one of which fits neatly into the major
groove of the DNA helix.

The shape of the homeodomain allows it to bind to any DNA segment; by itself it cannot
select a specific sequence.

Other more variable domains of such a protein determine which genes the protein
regulates. These other domains interact with transcription factors that help the protein
recognize specific enhancers or promoters in the DNA.
Different combinations of homeobox genes are active in different parts of the embryo.
In addition to homeotic genes, many other genes involved in development are highly conserved
from species to species. These include genes that control the components of many signaling
pathways.
“Homeoboxes are not restricted to homeotic genes and have been found in several other classes of developmentally
important genes. The amino acids encoded by the homeobox region contain a motif called a helix-turn-loop, which is
associated with binding to DNA sequences. Thus, a gene with a homeobox would be a prime candidate for a gene
that encodes a transcription factor.”
http://www.learner.org/channel/courses/biology/textbook/gendev/gendev_10.html
Other interesting sites:
http://gslc.genetics.utah.edu/units/basics/bodypatterns/similar.cfm
http://www.dhushara.com/book/evol/homeo/homeo.htm
http://www.learner.org/channel/courses/biology/textbook/gendev/gendev_6.html
http://www.learner.org/channel/courses/biology/textbook/gendev/index.html