CHAPTER 2

How development works

I. GAMETOGENESIS
A. Spermatogenesis
B. Oogenesis

II. FERTILIZATION, CLEAVAGE, BLASTULATION, GASTRULATION

III. FIVE MAIN PROCESSES OF DEVELOPMENTAL BIOLOGY

A. Regional specification
- from a population of similar cells, the formation
of a set of territories of cells each committed to become a
different structure or type ( ex. Head, trunk, tail)
B. Cell differentiation
- formation of specialized cells
C. Morphogenesis
- cell and tissue movements
D. Growth
-increase in size
E. Timing
- coordinated in time
II. FERTILIZATION, CLEAVAGE, BLASTULATION, GASTRULATION

Generalized sequence of early

development
II. FERTILIZATION- from the time of sperm entry to cleavage

Common features of fertilization

1. Block to Polyspermy - rapid change in egg structure that excludes

the fusion of any sperm

2. Activation of the Inositol triphosphate signal transduction pathway

Rapid increase in extracellular calcium

Causes exocytosis of cortical Increase rate of Trigger cytoplasmic

granules protein synthesis rearrangements that
position determinants
Start the second
Fertilization membrane meiotic division

ZYGOTE- fertilized egg; stage after the fusion of the male and female pronucleus
II. CLEAVAGE and BLASTULATION early cell division

-there is no growth phase between successive divisions

- Blastomeres product of cleavage

- The embryos own genome remains inactive during part or all of the cleavage
phase
- Protein synthesis is directed by mRNA transcribed during oogenesis

Maternal effects properties of the cleavage stage embryo

depends entirely on the genotype of the mother

TYPES OF CLEAVAGE

1. Meroblastic - part of the zygote cleaves, remainder ( e.g. yolk)

does not
2. Holoblastic - whole zygote becomes subdivided into
blastomeres
3. According to arrangement of blastomeres:
a. radial, bilateral, rotational, spiral superficial
BLASTULA, BLASTOCOEL, CADHERINS, TIGHT JUNCTIONS
Microlecithal / Oligolecithal - little yolk
- echinoderms, coelenterates,
amphioxus, mammals

Medialecithal / Mesolecithal - moderate amount of yolk

- annelids, mollusks, lampreys,
lungfishes, amphibians

Megalecithal/Macrolecithal - eggs have large quantities of yolk

- arthropods, hag fishes, bony
fishes, reptiles, birds, monotremes

Isolecithal- refers to an even distribution of yolk

Telolecithal- most of its yolk concentrated on one pole

- birds (highly), amphibians ( telolecithal)
III. GASTRULATION- phase of morphogenic movements in early development that
brings about the formation of the three germ layers

GASTRULA- three layered structure

Different processes during gastrulation

Invagination- infolding of a cell sheet to form an internal protrusion or pocket

- initiated from a localized apical constriction
- constriction causes the cell sheet to buckle -> constricted region of cells forms a
protrusion into the interior

Involution- internalization of a cell sheet by movement led by a free edge

- initiated from a localized apical constriction
- migration of cells around the edge of the constricted surface
- will involve the formation of a free edge in the involuting tissue

Epiboly active spreading and increase in area of a cell sheet

surface

sections
 Migration of cells Constricted region of
around the edge of cells forms a
the constricted protrusion in the
surface anterior

Sheets of cells surround and enclose another population

 GASTRULATION- convergent extension

Intercalation of cells leading to axial elongation ( convergent extension)

- Individual cells intercalate in between each other

- cause a constriction of the sheet in the direction of intercalation

- Elongation of the sheet at right angles to the intercalation

 GASTRULATION- Ingression

Ingression produces mesenchymal cells at the onset of gastrulation

- During the epithelial-mesenchymal transition (EMT), the primary

mesenchymal cells (PMCs) detach from the epithelium and become
internalized msenchymal cells that can migrate freely.

Lose its adhesion to hyaline, loses adhesion and

Cells lie scattered within
cadherin. Ingressing cells squeeze through the matrix
an extracellular matrix
or use protease
 REGIONAL SPECIFICATION and DETERMINANT

A. Regional specification
- from a population of similar cells, the formation
of a set of territories of cells each committed to become a
different structure or type ( ex. Head, trunk, tail)

Signaling
center

Determinant important for future regional specification of the embryo

- substance/s located in part of an egg or blastomere
- guarantees the assumption of a particular state of commitment
by the cells that inherit it during cleavage ( animation 4)
- can be mRNA o protein
- can be transcription factors
 REGIONAL SPECIFICATION and DETERMINANT

Determinants are of considerable importance for the very earliest stages of the
embryonic development. Often responsible for the establishment of the first two or three
distinctly specified regions in the embryo. Sometimes RNA or proteins. Becomes
expressed, localized and controls the fate of the first two blastomeres.
 REGIONAL SPECIFICATION and DETERMINANT

Generation of bilateral symmetry with two determinants

Two gradients partition the embryo into territories along two axes

The resulting embryo has territories arranged symmetrically around a

medial plane.
 Localization of a determinant by a symmetry breaking process

Localization of a determinant. Segregates some substances to one region of the

zygote and other substances to other regions.
 REGIONAL SPECIFICATION and DETERMINANT

PIE-1 - a bifunctional protein that regulates maternal and zygotic expression

- inhibit mRNA transcription
- promotes germ cell fate :
1. inhibition of transcription, which blocks zygotic programs that
drive somatic development
2. promotes primordial cell development by activating the protein
expression from nos-2 and possibly other maternal RNAs
REGIONAL SPECIFICATION and DETERMINANT

Germ cell during embryonic

development

1. Multiplication
2. Migration to the gonads
3. Become fully integrated
in the gonads
4. In mid-development- key
determination of sex
determination is made
5. Gonad is determined to
become ovary or testes
INDUCING FACTOR
Absence High
PROPERTIES OF A MORPHOGEN GRADIENT develops develops
head tail
Normal development of an animal
with head and three segments

Graft of the posterior source to

the anterior causes formation of a
U-shaped gradient and produces a
double-posterior animal.

Insertion of an impermeable
barrier causes formation of a
large gap in pattern

Morphogen- a type of inducing factor to

which competent cells can make at least
two different responses at different
threshold concentrations. Responding cell
will form a different committed territories .
 HOMEOTIC MUTANTS
Homeotic genes /selector genes
controls the commitment of different body parts
- a gene whose expression distinguishes two body parts. If mutated then
one body part will be converted into the other.
- Expression is controlled by cytoplasmic determinant or inducing factors

Normal genotype and

phenotype

Loss-of-function mutation
of gene 2 causes second
body segment to resemble
the first.

Gain-of-function mutation
of gene 2 causes first body
segment to resemble the
second.
DEVELOPMENTAL CONTROL GENES all encode transcription factors

BISTABLE SWITCH positive feedback on by a regulator ( either a

cytoplasmic determinant or a
regulation transduction pathway activated by
- Molecular mechanism which has two stable an inducing factor)
steady states that can be interconverted by
some external signal

The figure depicts a temporal sequence.

In step 2, the gene is upregulated by a
regulator
In step 3, it is also upregulated by its product
In step 4, it remains on because of the
product even though the regulator is gone
 AXES AND SYMMETRY

Principal
axes of
Anatomical
an planes of an
animal early embryo

Axes of a fertilized egg

after it has acquired a
dorsoventral symmetry

Ventral view of an animal showing

deviation from bilateral symmetry
 TYPES OF CELL MOVEMENTS

- Many morphogenic movements depend on the movement of individual cells

Long range ex. Migration of neural crest Short range ex. Adhesion or shape
cells or germ cells changes

1. Large flat Lamellipodia

2. Multiple Thin filipodia
3. Microfilament bundles

Flat process/ extension rich in

microfilaments

Apical constriction reduce the apical surface

area
- Increase the length of cells
- Preliminary to invagination
 CLASSIFICATION OF MORPHOGENIC MOVEMENTS
Localized apical
constriction

Migration of cells Constricted region of

around the edge of cells forms a
the constricted protrusion in the
surface anterior

-processes that generate multilayered structure from a single epithelium

- Found in gastrulation, neurulation, and in the formation of glands, sense
organs and appendages

Sheets of cells surround and enclose another population

- Expands to cover the whole embryo

CLASSIFICATION OF MORPHOGENIC MOVEMENTS

Cells form aggregates

ex. Somites and skeletal elements formation
- Arises partly by:
1. increased cell division
2. reduction of matrix secretion
3. increased cell-cell adhesion

generation of hollow ball or tube of cells

- May occur either by cell
rearrangement or by apoptosis of
cells in the interior
ex. Formation of lumen
 CLASSIFICATION OF MORPHOGENIC MOVEMENTS

Also called delamination

-cells leave epithelium and move off as -formation of coelomic lining of
individuals epithelium or of kidney tubules
-reduction in cell-cell adhesion in cells
Ex. Chick epiblast to form hypoblast
formation of neural crest from the dorsal
neural tube
CLASSIFICATION OF MORPHOGENIC MOVEMENTS

Individual cells intercalate in between

each other

- Causing constriction in the direction of

intercalation
And elongation of the sheet at right
angles to the intercalation

- Cells all need to be polarized in the

same direction

Acquisition of a polarity by cells in an

epithelium in the direction of the plane of
epithelium
- Found in most epidermal structures
CLASSIFICATION OF MORPHOGENIC MOVEMENTS

-characteristic of
organogenesis rather than
early development

- Epithelial bud grows into a

mesenchymal mass

- The number of growing

points progressively
increases to generate a
branched structure

- Ex. Tracheal system, lung or

kidney
 CELL ADHESION

Adhesion of early embryo cells is dominated by CADHERINS

Cadherin-based adhesion is homophilic- cells carrying E-cadherin will stick more
strongly than to cells bearing N-cadherin

If cells with different adhesion systems are mixed -> will sort out into separate
zones, eventually forming dumbbell-like configuration or even separate

with same adhesion systems : If cell type A is more adhesive than B, then B will
eventually surround A
 CELL ADHESION

Experiment demonstrating Cell sorting by differential adhesion

Red and green cells are colored with vital dyes

2.4 greater N-cadherin transfected in green cells

Cell types are Mixed together in an aggregate

More adhesive green cells in the middle

TYPES OF CELL DIVISION
 CONCEPT OF GROWTH

True growth increase in size

In later development, growth does not require an increase in cell number

Involve an increase in cell size

Increase in the amount of the extracellular matrix

* No real growth in free-living embryos

Xenopus, zebrafish or sea urchin
- Only caused by uptake of water

- Mammals, birds, reptiles with external

nutrient supply can grow extensively during
development
 Link for viewing animations online:

http://bcs.wiley.com/he-
bcs/Books?action=resource&bcsId=7612&itemId=0470923512&resourceId=29584
Fig. 47-14

ECTODERM MESODERM ENDODERM

Epidermis of skin and its Notochord Epithelial lining of

derivatives (including sweat
glands, hair follicles)
Epithelial lining of mouth
and anus
Cornea and lens of eye
Nervous system
Sensory receptors in
epidermis
Adrenal medulla
Tooth enamel
Epithelium of pineal and
pituitary glands
Skeletal system digestive tract
Muscular system Epithelial lining of
Muscular layer of respiratory system
stomach and intestine Lining of urethra, urinary
Excretory system bladder, and reproductive
Circulatory and lymphatic system
systems Liver
Reproductive system Pancreas
(except germ cells) Thymus
Dermis of skin Thyroid and parathyroid
Lining of body cavity glands
Adrenal cortex