Developmental Biology Reading Notes
Principles of Development 3 Edition – Lewis Wolpert
Chapter 1: History and Basic Concepts
I. Embryogenesis: the development of an embryo from the fertilized egg
A. First task = lay down overall body plan of the organism; different organisms
solve this in several ways.
B. Embryology: the study of developmental biology
C. Our understandings of the genetic control of development are most advanced in
Drosophilia melanogaster and Caenorhabditis elegans.
D. The study of developmental biology encompasses,
1. Development of the embryo
2. How animals can regenerate lost organs
3. Development of sexual characteristics
4. Control of post-embryonic growth
II. The Origins of Developmental Biology
A. Aristotle first defined the problem of epigenesis and performation
1. Aristotle explained the development of an embryo with two possible
a. Performation Theory of Development:
1 i. Everything in the embryo was performed from the very
beginning and simply got bigger during development.
b. Epigenesis Theory of Development: (his final theory)
i. New structures arise progressively in an embryo.
2. These two theories were subject to debate until it was realized that all
living things, including embryos, are composed of cells.
III. Cell Theory Changed the Conception of Embryonic Development and Heredity
A. Cell Theory: (1820-1880), by Schleiden and Schwann.
1. All living things consist of cells
2. Multicellular organisms can be viewed as communities of cells
3. Proved that development follows epigenesis, not performation, b/c during
development, many new cells are generated by division of the egg, and
new types of cells are formed.
4. The egg is a single, specialized cell.
5. Offspring does not inherit its characteristics from the body of the parent,
but only from the germ cells.
a. Characteristics acquired by the body during an animal’s life cannot
be transmitted to the germ line.
IV. Two Main Types of Development Were Originally Proposed Following the Cell
A. Once the embryo arose from the division of cells from the zygote, how did cells
B. Weismann’s Mosaic Mechanism for Development: the fate of each cell is
predetermined in the egg by the factors it would receive during cleavage.
1. Nucleus of the zygote contains many special factors called nuclear
2 2. While the fertilized egg underwent the rapid cycles of cell division,
known as cleavage, these nuclear determinants would be unequally
distributed to the daughter cells and would thus control the cell’s future
3. Must assume that early cell divisions must make the daughter cells quite
different from each other as a result of the unequal distribution of nuclear
4. Supporting Experiments: carried out by Wilhelm Roux
a. Observed frog embryos
b. After first cleavage, destroyed one of the two embryonic cells.
c. Remaining cell developed into a well-formed half-larva.
d. Concluded: Development of the frog is based on a mosaic
mechanism, the cells having their character and fate determined at
5. Non-Supporting Experiment: carried out by Hans Driesch
a. Separated the cells of an embryo at the two-cell stage and obtained
a normal, but small larva.
b. Opposite of Roux’s result.
c. The first demonstration of the developmental process called
regulation, the ability of the embryo to develop normally, even
when some portions are removed or rearranged.
i. Implies that cells must interact with each other.
V. The Discovery of Induction Showed the One Group of Cells Could Determine the
Fate of Neighboring Cells
A. Induction: phenomenon in which one cell, or tissue, directs the development of
another, neighboring, cell or tissue.
B. Supporting experiment: carried out by Spemann and Mangold
1. Transplant experiment in amphibian embryos
3 2. Showed that a partial second embryo could be induced by grafting one
small region of an early newt embryo onto another at the same stage.
3. The grafted tissue was taken from the blastopore, the slit-like
invagination that forms when gastrulation begins on the dorsal surface of
the amphibian embryo. This small region became called the organizer,
or Spemann organizer, since it seemed to be ultimately responsible for
controlling the organization of a complete embryonic body.
VI. The Study of Development was Stimulated by the Coming Together of Genetics and
A. At first, genetics and embryology seemed to be unrelated.
B. The distinction between genotype and phenotype helped link the two fields of
1. Individuals with the same genotype (identical twins) can develop
differences in their phenotypes.
2. Development problem now viewed as relationship between genotype and
phenotype: how the genetic endowment becomes expressed during
development to give rise to a functioning organism.
VII. Development is Studied Mainly ThroughASelection of Model Organisms
A. Studies of a relatively small number of model organisms has occurred because
once a certain amount of research has been done on one animal, it is more
efficient to continue to study that animal than to start at the beginning again with
B. Goal of Developmental Biology is to understand how genes control embryonic
development => need to identify genes critically involved in controlling
1. Via identification of mutations that alter development
C. Features of model organisms:
1. Diploid genome (X laevis is tetraploid)
2. Early age of reproduction (short breeding period)
4 3. Sexually reproduce
4. Able to produce transgenic organisms upon genetic manipulation.
D. When an important developmental gene has been found in one organism, it is
important to consider whether a corresponding gene is present and acting in a
developmental capacity in other animals.
1. These genes, called homologous genes, are identified by a sufficient
degree of nucleotide sequence similarity, which also indicates descent
from a common ancestral gene.
VIII. The First Developmental Genes Were Identified as Spontaneous Mutations
A. Dominant and semi-dominant mutations are those that produce a distinct
phenotype when the mutation is present in just one of the alleles of a pair.
1. Dominant mutations are usually lethal.
2. Dominant mutations are easier to identify , provided they do not cause the
early death of the organism
B. Identifying recessive mutations is harder and requires careful observation and
analysis in mammals, as the homozygotes may die unnoticed in the mother.
C. Need to be able to distinguish mutations of genes that directly affect
development versus genes involved in housekeeping functions, such as the
production of energy and metabolic pathways involved in the breakdown and
synthesis of molecules necessary for the life of the cell.
1. Mutations resulting in embryonic death may fall under either category.
2. Mutations that produce abnormal patterns of development = mutations of
genes responsible for development
D. Developmental genes typically code for proteins involved in the regulation of
2. Growth factors
3. Intracellular signaling proteins
4. Gene-regulatory proteins
5 IX. ThereAre 6 Main Developmental Processes
A. Cleavage: the division of the fertilized egg into many smaller cells.
1. No increase in cell mass between each cleavage division.
2. DNArep, mitosis, cell division w/ no cell growth stage.
B. Pattern formation: process by which a spatial and temporal pattern of cellular
activities is organized within the embryo => well ordered structure develops.
1. Initially involves forming the overall body plan, defining the main axes
of the embryo so that the anterior, posterior, dorsal, and ventral sides are
a. Antero-posterior axis: the main body axis, which runs from head
b. Dorso-ventro axis: runs from back to belly; in bilaterally
c. Occurs early in development
2. Even before axes become clear, embryos show distinct polarity.
C. Allocation of cells to the different germ layers - the ectoderm, mesoderm, and
1. Cells of these germ layers acquire different identities so that organized
spatial patterns of cell differentiation emerge.
a. Ex: the arrangement of skin, muscle and cartilage in developing
limbs; the arrangement of neurons in the nervous system.
D. Morphogenesis: a change in 3D form
1. Involves extensive cell migration
2. Gastrulation: a form of morphogenesis undergone by most animals
a. The gut is formed and the body plan emerges
E. Cell differentiation: cells become structurally and functionally different from
each other, ending up as distinct cell types
6 1. Ex: Blood, muscle, or skin cells
2. Gradual process, may span over several cycles of cell division
3. Interrelated with pattern formation
F. Growth: an increase in embryo size
1. Little growth during embryonic development
2. Subsequent growth can be brought about in many ways:
a. Cell multiplication
b. Increase in cell size
c. Formation of extracellular materials (i.e. bone and shell)
3. Growth can be morphogenic ~ differences between growth rates of
different parts of the body can generate changes in the overall shape of
X. Cell Behavior Provides the Link Between GeneAction and Developmental
A. Categories of cell behavior, dependent on the variation in gene expression, that
1. Cell-cell signaling
a. Spemann organizer example
2. Changes in cell shape
a. Cells generate physical forces that lead to morphogenesis
i. Ex:Alocalized contraction can cause a whole sheet of cells
3. Cell movement
4. Cell proliferation
5. Cell death
B. Cell surface proteins are important for,
7 1. Holding cells together in tissues
2. Sensing environment
3. Guide migratory cells that form structures elsewhere in the body
XI. Genes Control Cell Behavior by Specifying Which Proteins are Made
A. In development, we are concerned with tissue-specific proteins that make cells
different from one another.
B. Factors determining which proteins are produced:
1. mRNA control
a. Nuclear degredation
b. Cytoplasmic inactivation
2. RNA processing
3. Post-translational modification of proteins
XII. The Expression of Developmental Genes is Under the Control of Complex Control
A. With only a few rare exceptions, all somatic cells contain the same genetic
information as the zygote.
1. Differences in cells due to the different expression of genes => proteins
a. Variation in gene expression is regulated by the control regions
located adjacent to most developmental genes.
b. Gene regulatory proteins, or transcription factors, activate or
repress transcription by binding to control regions or other
transcription factors already bound to the DNA.
i. Usually work in positive feedback and negative feedback
8 c. Developmental genes contain many transcription factors
d. Genes having the same control module will usually be expressed
B. Gene expression is only the first step of many cellular processes that lead to
changes in cell behavior (via protein synthesis) and direct the course of
1. Cannot think of development simply in terms of controlling gene
XIII. Development is Progressive and the Fate of Cells Becomes Determined at Different
A. The embryo is first divided into a few broad regions, such as the future germ
1. The cells within these layers have their fates more finely determined.
B. Determination: implies a stable change in the internal state of a cell, and an
alteration in the pattern of gene activity is assumed to be the initial step, leading
to a change in the proteins produced in the cell.
C. The fate of a cell merely describes what type of cell it will develop into.
D. Agroup of cells is called specified if, when isolated and cultured in the neutral
environment of a simple culture medium (lacking any inducing signals) away
from the embryo they develop according to their normal fate.
E. The state of determination of cells at any developmental stage can be
demonstrated by transplantation experiments.
1. Cells from one region grafted to another region can develop according to
their new position, only if they are at an early stage of development and
are not yet determined.
a. Cells in the early embryo are less narrowly determined than those
at later stages
b. With time, cells become more restricted in the developmental
c. The change in genes expressed restricts cell’s fate
9 F. Regulative embryos: cells do not seem to be determined in the early embryo.
1. Potential of cells is > than that indicated by their normal fate
2. Seen among vertebrate embryos
G. Mosaic embryos: cells can develop only according to their fate from a very
1. Determination occurs much earlier than it does in regulative embryos
XIV. Inductive Interactions Can Make Cells Different From Each Other
A. Induction: signals from one group of cells influences the development of an
adjacent group of cells; can alter how induced cells develop.
1. Ex: Spemann organizer
2. May be highly localized or propagated over many cells
3. Permissive induction: occurs when a cell makes only one kind of
response to a signal, and makes it when a given level of signal is reached.
4. Instructive induction: the cell responds differently to different
concentrations of the signal.
B. Three ways for inducing signals to be passed between cells:
1. Signal may be transmitted thru extracellular space via secretion of a
2. Cells may interact directly via cell surface proteins
3. Signal may pass from cell to cell directly via gap junctions
C. Signal transduction: process by which a signal is transmitted from the cell
membrane to the cell interior in order to ultimately alter gene expression.
1. Also used to temporarily alter enzyme activity and metabolic activity and
relay nerve impulses.
2. Carried out by relays of intracellular signaling molecules that are
activated when the extracellular signal molecule binds to its receptor.
10 3. Most signaling dealing with development leads to gene activation or
D. An important feature of induction is whether or not the responding cell is
competent to respond to the inducing signal.
1. Competence may depend upon the presence of the appropriate:
b. Transducing mechanism
c. Transcription factors needed for gene activation
2. Acell’s competence for a particular response may change with time.
E. After receiving an inductive signal, a cell usually then develops autonomously,
without new signals from another cell, for some time.
F. An inductive signal selects one out of several possible responses.
1. Different signals can activate a particular gene at different stages of
a. The same gene is often turned Off and on many times throughout
2. The same signal can be