DEVELOPMENTAL BIOLOGY

What is it?

Three definitions;

i. Developmental Biology is the study of the processes by which organs grow and develop.
Modern developmental biology studies the genetic control of cell growth, differentiation
and morphogenesis, which is the process that gives rise to tissues, organs and anatomy,
but also regeneration and ageing (after L. Wolpert)
ii. Developmental biology is the study of the process by which animals and plants grow and
develop, and is synonymous with ontogeny (Wikipedia).
iii. Developmental Biology is the causal analysis of the cellular mechanisms that drive
processes of growth, pattern formation and morphogenesis (A. Martínez Arias)

It represents an exemplary area of contemporary experimental biology that focuses on

phenomena that have puzzled natural philosophers and scientists for more than two millennia.
Philosophers of biology have shown renewed interest in developmental biology due to the
potential relevance of development for understanding evolution, the theme of reductionism in
genetic explanations, and via increased attention to the details of particular research programs.
Developmental biology displays a rich array of material and conceptual practices that can be
analyzed to better understand the scientific reasoning exhibited in experimental life science.

Developmental biology is a great field for scientists who want to integrate different levels of
biology. We can take a problem and study it on the molecular and chemical levels (e.g., How are
globin genes transcribed, and how do the factors activating their transcription interact with one
another on the DNA?), on the cellular and tissue levels (Which cells are able to make globin, and
how does globin mRNA leave the nucleus?), on the organ and organ system levels (How do the
capillaries form in each tissue, and how are they instructed to branch and connect?), and even at
the ecological and evolutionary levels (How do differences in globin gene activation enable
oxygen to flow from mother to fetus, and how do environmental factors trigger the
differentiation of more red blood cells?).

Developmental biology is one of the fastest growing and most exciting fields in biology, creating
a framework that integrates molecular biology, physiology, cell biology, anatomy, cancer
research, neurobiology, immunology, ecology, and evolutionary biology. The study of
development has become essential for understanding any other area of biology.

Why Study Developmental Biology?

According to Aristotle, (the first embryologist known to history), science begins with wonder:
“It is owing to wonder that people began to philosophize, and wonder remains the beginning of
knowledge.” The development of an animal from an egg has been a source of wonder throughout
history. The simple procedure of cracking open a chick egg on each successive day of its 3-week
incubation provides a remarkable experience as a thin band of cells is seen to give rise to an
entire bird. Aristotle performed this procedure and noted the formation of the major organs.
Anyone can wonder at this remarkable—yet commonplace—phenomenon, but the scientist seeks
to discover how development actually occurs. And rather than dissipating wonder, new
understanding increases it.

Multicellular organisms do not spring forth fully formed. Rather, they arise by a relatively slow
process of progressive change that we call development. In nearly all cases, the development of
a multicellular organism begins with a single cell—the fertilized egg, or zygote, which divides
mitotically to produce all the cells of the body. The study of animal development has
traditionally been called embryology, from that stage of an organism that exists between
fertilization and birth. But development does not stop at birth, or even at adulthood.

Most organisms never stop developing. Each day we replace more than a gram of skin cells (the
older cells being sloughed off as we move), and our bone marrow sustains the development of
millions of new red blood cells every minute of our lives. In addition, some animals can
regenerate severed parts, and many species undero metamorphosis (such as the transformation of
a tadpole into a frog, or a caterpillar into a butterfly). Therefore, in recent years it has become
customary to speak of developmental biology as the discipline that studies embryonic and other
developmental processes.

Development accomplishes two major objectives: it generates cellular diversity and order within
each generation, and it ensures the continuity of life from one generation to the next. Thus, there
are two fundamental questions in developmental biology: How does the fertilized egg give rise to
the adult body, and how does that adult body produce yet another body? These two huge
questions have been subdivided into six general questions scrutinized by developmental
biologists:
1. The question of differentiation. A single cell, the fertilized egg, gives rise to hundreds
of different cell types—muscle cells, epidermal cells, neurons, lens cells, lymphocytes,
blood cells, fat cells, and so on. This generation of cellular diversity is called
differentiation. Since each cell of the body (with very few exceptions) contains the same
set of genes, we need to understand how this same set of genetic instructions can produce
different types of cells. How can the fertilized egg generate so many different cell types?
2. The question of morphogenesis. Our differentiated cells are not randomly distributed.
Rather, they are organized into intricate tissues and organs. These organs are arranged in
a given way: the fingers are always at the tips of our hands, never in the middle; the eyes
are always in our heads, not in our toes or gut. This creation of ordered form is called
morphogenesis. How can the cells form such ordered structures?
3. The question of growth. How do our cells know when to stop dividing? If each cell in
our face were to undergo just one more cell division, we would be considered horribly
malformed. If each cell in our arms underwent just one more round of cell division, we
 could tie our shoelaces without bending over. Our arms are generally the same size on
both sides of the body. How is cell division so tightly regulated?
4. The question of reproduction. The sperm and egg are very specialized cells. Only they
can transmit the instructions for making an organism from one generation to the next.
How are these cells set apart to form the next generation, and what are the instructions in
the nucleus and cytoplasm that allow them to function this way?
5. The question of evolution. Evolution involves inherited changes in development. When
we say that today's one-toed horse had a five-toed ancestor, we are saying that changes in
the development of cartilage and muscles occurred over many generations in the embryos
of the horse's ancestors. How do changes in development create new body forms? Which
heritable changes are possible, given the constraints imposed by the necessity of the
organism to survive as it develops?
6. The question of environmental integration. The development of many organisms is
influenced by cues from the environment. Certain butterflies, for instance, inherit the
ability to produce different wing colors based on the temperature or the amount of
daylight experienced by the caterpillar before it undergoes metamorphosis. How is the
development of an organism integrated into the larger context of its habitat?

MODEL ORGANISMS IN DEVELOPMENTAL STUDIES

A model organism is a non-human species that is extensively studied to understand particular
biological phenomena, with the expectation that discoveries made in the model organism will
provide insight into the workings of other organisms.

Model organisms are in vivo models and are widely used to research human disease when human
experimentation would be unfeasible or unethical. This strategy is made possible by the common
descent of all living organisms, and the conservation of metabolic and developmental pathways
and genetic material over the course of evolution.

Studying model organisms can be informative, but care must be taken when extrapolating from
one organism to another.

In researching human disease, model organisms allow for better understanding the disease
process without the added risk of harming an actual human. The species chosen will usually meet
a determined taxonomic equivalency to humans, so as to react to disease or its treatment in a way
that resembles human physiology as needed. Although biological activity in a model organism
does not ensure an effect in humans, many drugs, treatments and cures for human diseases are
developed in part with the guidance of animal models. There are three main types of disease
models: homologous, isomorphic and predictive. Homologous animals have the same causes,
symptoms and treatment options as would humans who have the same disease. Isomorphic
animals share the same symptoms and treatments. Predictive models are similar to a particular
human disease in only a couple of aspects, but are useful in isolating and making predictions
about mechanisms of a set of disease features

Model organisms have been important throughout the study of modern biology. In the 1940s and
1950s, biochemical analysis of bacteria was important in working out the enzymatic pathways of
metabolism. In the 1960s and 1970s, bacteria, especially Escherichia coli and its viruses (called
phages), provided models for the new science of molecular biology and the elucidation of basic
mechanisms for deoxyribonucleic acid (DNA) replication, transcription, and translation in
prokaryotes.

Since then, the budding yeast Saccharomyces cerevisiae and more recently the fission yeast
Schizosaccharomyces pombe have served as models for intensively investigating the molecular
mechanisms of these and other functions unique to eukaryotic cells, such as the cdk-cyclin-based
cell cycle, mitosis, meiosis, ribonucleic acid (RNA) splicing, regulation of chromatin structure,
secretion, dynamics of the cytoskeleton, stress pathways, checkpoint pathways, and, to some
degree, intercellular signaling and differentiation, the last two associated with yeast mating.

Most of these cellular functions have been highly conserved during eukaryotic evolution, so that
knowledge gained from yeast research is directly applicable to understanding human cell
processes. However, understanding the interactions of cells and tissues in development and
physiology of higher eukaryotes requires study of metazoans (i.e., multicellular animals).

It should be appreciated, though, that as the processes are understood in metazoa, the
components of each process can be introduced into yeast and the individual processes
reconstituted there for further detailed study. For example, it has been found that a number of
human cell-cycle proteins function well in the yeast cell cycle, when replacing the yeast cell’s
components.

Why use model Organisms?

Much has been learned about human development and physiology through
the study of model animals, a small set of diverse metazoans that have
particular advantages for laboratory research. There are several reasons for
their utility.

Research on humans and other primates is expensive and limited by ethical

considerations. The most commonly studied model animals are relatively
inexpensive to maintain and are well suited for experimental manipulation.
Recent research has shown that there is a remarkable degree of similarity in
the developmental mechanisms of all animals. Not only individual genes and
proteins but also entire pathways of signaling and response and their
functions in developing embryos appear highly conserved throughout
evolution. This means that, although the embryology of simpler animals
might appear superficially very different from that of humans, knowledge
gained from those models can often be applied directly to understanding
human developmental mechanisms.

On the other hand, there are important developmental and physiological

attributes that can be investigated only in vertebrates, such as the adaptive
immune system, or in mammals, such as placentation and lactation.
Therefore, it is useful to study a representative range of model animals—
from invertebrates that are only distantly related to humans but have
particular experimental advantages, to rodents and other mammals that are
less convenient but more closely related to humans.

Model Animals for Study of Development

For study of development, the currently most intensively investigated model animals, in order of
increasing complexity, are;
i. The free-living soil roundworm (nematode) Caenorhabditis elegans
ii. The fruit fly Drosophila melanogaster
iii. The frog Xenopus laevis
iv. The zebrafish Danio rerio
v. The chick
vi. The laboratory mouse (Mus musculus)
Others include sea urchin, sea slug (Aplysia), puffer fish, and a few mammals, including the rat.

This set of model animals is somewhat different from those most widely used in the 1950s. Why
have these species been chosen for recent intensive study? For four of them, the principal answer
is genetics.
The genetic approach has become established in the last three decades as one of the most
powerful tools for elucidating biological mechanisms. It allows researchers to compare wild type
with a mutant phenotype and to identify new genes involved in controlling a biological process
and to determine their functions in the organism. Genes that control important functions are
identified by mutations that cause defects in those functions. These genes are then mapped,
cloned, and identified at the molecular level so that the proteins they encode can be studied using
methods of biochemistry and cell biology. This approach has proved to be extremely powerful,
not only for basic research in model organisms but also for medical research on heritable human
diseases. The approach was followed, for example, in the mapping, cloning, and subsequent
study of the cystic fibrosis gene, the breast cancer susceptibility gene, and many others.

The four model animals chosen primarily on the basis of their convenience for genetic analysis
are C. elegans, Drosophila, zebrafish, and mice. All are relatively small, easy to maintain in
large populations in the laboratory, and have short generation times, which allow for rapid
analysis of breeding experiments.

The remaining animals are not well suited for classical genetic analysis, primarily because of
much longer generation times, but have compensating advantages of convenience and
manipulability or simplicity. Sea urchins, because of their reproductive properties, have been
particularly valuable in studies of fertilization and gene regulation in early embryos.

Aplysia are used in nerve growth and development studies. Puffer fish are useful for genomics
because of their remarkably small genome size (400 megabases (Mb)) compared with most other
vertebrates (about 3,500 Mb, including humans).

The frog Xenopus has eggs and embryos that can be obtained in quantity and are relatively large
(about 1 millimeter (mm) in diameter). The eggs and embryos are convenient for biochemical
analysis as well as microsurgery and can easily be microinjected with cloned genes, RNAs,
proteins, drugs, and so forth to study the developmental effects of those molecules. The embryos
have been used in toxicant tests, such as the frog embryo teratogenesis assay–Xenopus (FETAX).
FETAX is currently under consideration for validation.

Chick embryos (more closely related to mammalian embryos),are readily accessible for
observation and microsurgery (unlike those of mice, which develop in the uterus) and are
convenient for tissue transplantation experiments. Putative developmental toxicants can be added
directly to the embryo, thereby bypassing the modifying effects of maternal metabolism and
selective transfer by the placenta.

Rat, rabbit, and guinea pig have long been standard systems for physiological and toxicological
investigation. However, because of the power of genetic analysis, the four genetically tractable
model animals (C. elegans, Drosophila, zebrafish, and mouse) have become mainstays of recent
research in developmental biology and, for the same reason, are also likely to be particularly
valuable in emerging approaches to developmental toxicology.
In Summary