Download Lecture 1 Introduction to DEVELOPMENTAL

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Introduction to developmentHow does an organism go from a single cell to something as
complex as a frog, fly, or human being? Learn the basic principles of development.
Introduction
You, my friend, are a walking, talking, thinking, learning collection of
over 303030 \text{trillion}trillionstart text, t, r, i, l, l, i, o, n, end text cells^11start superscript,
1, end superscript. But you weren’t always that large and complex. In fact, you (like every
other human on the planet) started out as a single cell – a zygote, or the product of
fertilization. So, how did your amazing, complex body form?
Development: The big picture
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.
As an embryo develops, its cells divide, grow, and migrate in specific patterns to make a
more and more elaborate body. To function correctly, that body needs welldefined axes (such as head vs. tail). It also needs a specific collection of manycelled organs and other structures, positioned in the right spots along the axes and connected
up with one another in the right ways.
The cells of an organism's body must also specialize into many functionally different types as
development goes on. Your body (or even the body of a newborn) contains a wide array of
different cell types, from neurons to liver cells to blood cells. Each one of these cell types is
found only in certain parts of the body—in certain tissues of certain organs—where its
function is needed.
How does this intricate cellular dance unfold? Development is largely under the control of
genes. Mature cell types of the body, like neurons and liver cells, express different sets of
genes, which give them their unique properties and functions. In the same way,
cells during development also express specific sets of genes. These patterns of gene
expression guide cells’ behavior and allow them to communicate with neighboring cells,
coordinating development.
In this article and the ones that follow, we’ll take a closer look at principles and examples of
development.
Some basic processes of development
Different organisms develop in different ways, but there are some basic things that must
happen during the embryonic development of almost any organism:
The number of cells must increase through division
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Body axes (head-tail, right-left, etc.) must form
Diagram based on frog life cycle diagram from Xenbase^22squared.
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Tissues must form, and organs and structures must take on their shapes
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Diagram based on frog life cycle diagram from Xenbase^22squared.
Individual cells must acquire their final cell type identities (e.g., neuron)
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To be clear, these processes aren’t separate events that happen one after another. Instead, they
are going on at the same time as the embryo develops.
For instance, different body axes (such as head-tail and left-right) are set up at different times
during early development, while the cells of the embryo are dividing away in the background.
Similarly, formation of an organ requires cell division to build that organ, as well
as differentiation (cells taking on their final identities) to ensure that the right cells make up
the right parts of the organ.
Sources of information in development
How do cells know what they're supposed to do during development? That is, how does a cell
know when and how to migrate, divide, or differentiate? Broadly speaking, there are two
kinds of information that guide cells' behavior:
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 cellproducing, 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).
During development, cells often use both intrinsic and extrinsic information to make
decisions about their identity and behavior. Of course, they don't actually "decide" by
thinking the problem over like you or me! Instead, cells make decisions in the way a
calculator or computer would: by using genes and proteins to perform logic operations
that calculate the best response.
Differentiation, determination, and stem cells
Over the course of development, cells tend to become more and more restricted in their
"developmental potential." ^33cubed That is, the types of other cells they can make by cell
division (or directly turn into) become fewer and fewer.
For instance, a human zygote can give rise to all the cell types of the human body, as well as
the cells that make up the placenta. To use vocab from the stem cell field, this ability to give
rise to all cell types of the body and placenta makes the zygote totipotent. However, after
multiple rounds of cell division, the cells of the embryo lose their ability to give rise to cells
of the placenta and become more restricted in their potential (pluripotent)^44start
superscript, 4, end superscript. These changes are due to alterations in the set of genes
expressed in the cells.
Eventually, the cells of the embryo are split into three different groups known as germ
layers: mesoderm, endoderm, and ectoderm. Each germ layer will, under normal conditions,
give rise to its own specific set of tissues and organs.
As the cells of a germ layer continue to divide, interacting with their neighbors and reading
out their own internal information, their cell fate “options” will get narrower and narrower.
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^55start superscript, 5, end
superscript.
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.
Left panel: liver cell. The liver cell contains alcohol dehydrogenase proteins. If we look in the
nucleus, we see that an alcohol dehydrogenase gene is expressed to make RNA, while a
neurotransmitter gene is not. The RNA is processed and translated, which is why the alcohol
dehydrogenase proteins are found in the cell.
Right panel: neuron. The neuron contains neurotransmitter proteins. If we look in the nucleus,
we see that the alcohol dehydrogenase gene is not expressed to make RNA, while the
neurotransmitter gene is. The RNA is processed and translated, which is why the
neurotransmitter proteins are found in the cell.
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.
Adult stem cells
Not all cells in the human body differentiate. Some cells in the adult body retain the ability to
divide and produce multiple cell types. These include adult stem cells, which are
usually multipotent: they can produce more than one cell type, but not a large range of cell
types^44start superscript, 4, end superscript. For instance, hematopoietic stem cells in the
bone marrow can give rise to all the cell types of the blood system (shown below), but not
other cell types such as neurons or skin cells.
The hallmark of stem cells is that they undergo asymmetric cell division, producing two
daughter cells that are different from one another. One daughter remains a stem cell, a
process called self-renewal (the dividing cell "renews" itself by making a functionally
identical daughter). The other daughter cell takes on a different identity, either differentiating
directly into a needed cell type or going through additional divisions to make more cells.
Developmental genetics
Developmental genetics is the study of how genes control the growth and development of an
organism throughout its life-cycle.
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Genes code for proteins, and proteins build bodies: a salmon fry hatching from an egg.
The function of genes is to pass on the information necessary to build proteins - and bodies from one generation to the next. A newly fertilised egg cell has a collection of genes that
contains all information needed to transform it from a single cell into an embryo and then an
adult. The process that changes a single cell into a new person (or a new frog, or a new oak
tree) is called development.
During the course of development, complex structures develop from simple ones. A single
cell transforms itself into an adult organism. How does something complicated come from
something simple? And how do genes control this process?
Creating an organism from a single cell involves three important processes:
Cell division: cells divide to produce more cells.
Cell differentiation: cells change into different types of cell to do specific jobs in the body,
from nerve cells to muscle cells.
Morphogenesis: groups of cells move and change their shape to produce the structure of the
organism.
Genes play a vital role in controlling all of these processes.
Genes contain the information a cell needs to make proteins - a bit like a recipe for a living
thing. Different genes contain the information needed to make different proteins, and
different proteins do different jobs in the cell. The proteins a cell makes decide what kind of
cell it becomes, and there are some 350 different types of cell in an adult human being.
Cells change into different types of cell because of changes in the way their genes work.
Some genes are activated (switched on), and some genes are inactivated (switched off). As a
result, the cell produces a specific set of proteins. So, for example, a nerve cell produces only
the proteins needed to make a nerve cell, and a muscle cell produces only the proteins needed
to make a muscle cell.
But how do cells switch their genes on and off? And, more importantly, how do they 'know'
which genes to switch on and which genes to switch off? The answer lies in special control
genes that produce proteins that control the activity of other genes. So, for
example, homeotic or homeobox genes control whole sets of other genes to set out the basic
body plan of the embryo, separating the front from the back, and producing the right body
structure in the right place.
One way in which genes can influence the activity of other genes is through the production of
proteins called transcription factors, which stick to special control sites in the DNA at the
start of a gene to switch them on and off. (See Gene expression and regulation for more
details.)