Developmental Biology

1. Advanced Developmental Biology

2. A. "Unity of Type" and "Conditions of
Existence“
B. Hox Genes: Descent with Modification
C. Homologous Pathways of Development
D. Modularity: The Prerequisite for
Evolution through Development
E. Developmental Correlation
F. Developmental Constraints
G. A New Evolutionary Synthesis

3. 1. Differences among species that allowed
each species to adapt to its
environment ("conditions of existence.“)
2. Adaptations were secondary, and that
the "unity of type ("homologies") was
critical.
*”Evolution consists of modifying
embryonic organisms, not adult ones”
(Metchnikoff,1891).

4. • Unity of type= descent from common
ancestor
• Conditions of existence= natural
selection
• *common descent- embryonic
homologies
• *modification- showing how
development was altered to produce
structures that enabled animals to adapt
to particular condition

5. 1. To find the underlying unities that link
disparate groups of animals,
2. To detect those differences in
development that enable species to
adapt to particular environments.

7. • Urbilaterian ancestor/ PDA
(protostome-deuterostome ancestor)
– Hypothetical ancestor
– Had neither endoskeleton(deu.) or hard
exoskeleton( proto.)
“Paleontology without fossil”
• to find homologous genes that are
performing the same functions in both
a deuterostome (usually a chick or a
mouse) and a protostome (generally
an arthropod such as Drosophila).

8. • Pax6- plays a role in forming eyes in
both vertebrates and invertebrates
• Tinman/Nkx2 5- involved in heart
formation in deuto. and proto.
• tailless (tll) ,orthodenticle (otd) and
empty spiracles (ems)/(Otx-1, Otx-
2,Emx-1,Emx-2)- genes encoding for
transcription factors involved in head
formation

9. • Hox genes- basis of anterior-posterior
axis specification throughout the animal
kingdom
• If the underlying Hox gene expression is
uniform, how did the differences among
the phyla emerge?
– Arose from differences in how the Hox genes
are regulated and what target genes the
Hox-encoded proteins regulate.

10. 1. Changes in the Hox protein-responsive
elements of downstream genes
2. Changes in Hox gene transcription
patterns within a portion of the body
3. Changes in Hox gene transcription
patterns between portions of the body
4. Changes in the number of Hox genes

11. -Changes in the genes hox proteins
regulate.
Ultrabithorax gene (Ubx)-expressed in the
imaginal disc of the third thoracic
segment(wing or haltere are dericed)
Drosophila- Ubx downregulate several
genes in the imaginal disc
Butterfly- Genes regulated in Drosophila
are not regulated in butterfly

12. • Distal-less (Dll) gene is critical for
providing the proximal-distal axis of the
appendages
• Distal-less expression occurs in the
cephalic and thoracic limb-forming discs,
but it is excluded in the abdomen by the
abdA and Ubx proteins.
• Dll (in thorax and cephalic)= limb and
wing(thorax) and jaw (head) formation
• Dll inhibited by abdA and Ubx (in
abdomen) = no legs will form

13. A. Origins of maxillipeds in
crustaceans
• Antp,Ubx, and abdA are
expressed in the thorax=
mirror thoracic segments
• if a thoracic segment does
not express Ubx and abdA, it
converts its anterior
locomotor limb into a
feeding appendage called a
maxilliped

14. B.Why snakes don’t have legs
Thoracic vertebrae= have ribs
Cervical and lumbar= no ribs
*the type of vertebra produced is specified
By the hox genes expressed in the somites

15. • the forelimb forms just anterior to the most
anterior expression domain of Hoxc-6
• hoxc6 + hoxc8= thoracic vertebrae forms ribs
• During early python development, Hoxc-6 is
not expressed in the absence of Hoxc-8, so
the forelimbs do not form. Rather, the
combination of Hoxc-6 and Hoxc-8 is
expressed for most of the length of the
organism, telling the vertebrae to form ribs
throughout most of the body

16. • The hindlimb buds do begin to form in
pythons, but they do not make
anything more than a femur. This
appears to be due to the lack of sonic
hedgehog expression by the limb bud
mesenchyme.
• Sonic hedgehog is needed both for the
polarity of the limb and for
maintenance of the apical ectodermal
ridge (AER). Python hindlimb buds lack
the AER.

17. • Invertebrates – single hox gene
complex per haploid genome.
– sponges- have one or two genes in the
complex
– Insects have numerous genes in the
complex
• Early vertebrate- at least 4 hox gene
complex

18. • How does a new cell type form?
-involves the duplication and divergence of
genes.
Example:
Dll gene originally has only one copy in
Amphioxus but have about 5-6 closely
related copies in vertebrates.
The Dll homologues have found new
functions in modern vertebrates;
a. Expressed in mesoderm
b. Expressed in forebrain
• Although it remains unproven, it is possible that the
new type of Distal-less gene could have caused the
migratory ectodermal cells of amphioxus to evolve
into neural crest cells.

19. • Homologous transduction pathways
• They are composed of homologous
proteins arranged in a homologous
manner.
• Homologous pathways form the basic
infrastructure of development. The
targets of these pathways may differ,
however, among organisms.

20. 1. Dorsal-Cactus Pathway
Drosophila- specify dorsal-ventral polarity
Mammal- activate inflammatory protein
The pathways (one in Drosophila, one in
humans) are homologous; the organs
they form are not.
2. RTK pathway
Drosophila- photoreceptor
Mammal- epidermal cell division
C.elegans- vulval differentiation and
division

21. • When homologous pathways made of
homologous parts are used for the same
function in both protostomes and
deuterostomes
Example:
Chordin/BMP4 pathway
demonstrates that in both vertebrates and
invertebrates, chordin/Short-gastrulation (Sog)
inhibits the lateralizing effects of
BMP4/Decapentaplegic (Dpp), thereby allowing
the ectoderm protected by chordin/Sog to
become the neurogenic ectoderm.
*High chordin/Sog= low BMP4/Dpp= ectoderm develop to
neurogenic cell
*Low chordin/Sog= high BMP4/Dpp= ectoderm develop to
epidermal cell

22. • How can the development of an
embryo change when development is
so finely tuned and complex?
• How can such change occur without
destroying the entire organism?

23. • Organisms are constructed of units that are coherent within
themselves and yet part of a larger unit. Thus, cells are parts
of tissues, which are parts of organs, which are parts of
systems, and so on.
• In development, such modules include
a. morphogenetic fields (for example, those described for the
limb or eye)
b. pathways (such as those mentioned above), imaginal discs,
c. cell lineages (such as the inner cell mass or trophoblast),
d. insect parasegments, and
e. vertebrate organ rudiments.
Modular units allow certain parts of the body to
change without interfering with the functions of other parts.

24. 1. Dissociation
– Not all part of the embryo is connected to one
another
a. Heterochrony - shift in the relative timing of
two developmental processes from one
generation to the next. In other words, one
module can change its time of expression
relative to the other modules of the embryo.
CAUSES
1. gene mutations in the ability to induce or
respond to the hormones initiating
metamorphosis
2. heterochronic expression of certain genes.

25. b. Allometry- growth of different
part at different rates
Example:
Whale skull vs human skull

26. 2. Duplication and Divergence
a) duplication part of this process allows
the formation of redundant structures,
b) divergence part allows these structures
to assume new roles.
Example:
1. Hox genes
2. TGF-β family genes,
3. MyoD family genes, and
4. Globin genes
5. Duplication and divergence in the somites
that give rise to the cervical, thoracic, and
lumbar vertebrae.

27. 3. Co-option
– No one structure is destined for any particular
purpose
– A pencil can be used for writing, but it can also
be used as a toothpick, a dagger, a hole-
puncher, or a drumstick.
Example:
1. Engrailed gene
• Segmentation in drosophila
• Specification of neurons
• Provide anterior-posterior axis
2. Enolase or alcohol dehydrogenase
• Enzyme in liver
• Structural crystaline protein in lens
*In other words, preexisting units can be co-
opted (recruited) for new functions.

28. A. Correlated Progression
– changes in one part of the embryo
induce changes in another.
Example:
Skeletal cartilage informs the placement of
muscles, and muscles induce the
placement of nerve axons. In such cases,
if one structure changes, it will induce
other structures to change with it.

30. B. Coevolution of ligand and receptor
• Ligands have to fit with receptors, and
they have to be expressed at the right
place and at the right time.
• Changes in the ligand must be
accommodated by complementary
changes in the receptor if the receptor is
to function.
• If a mutation in a gene encoding ligand (or
receptor) produces too great a change, it
will not bind to its complementary
receptor (or ligand), and development will
stop. When duplications of ligand and
receptor genes occur, they can diverge and
acquire new functions.

31. 1. Physical constraints
– The laws of diffusion, hydraulics, and
physical support allow only certain
mechanisms of development to occur.
Example:
Structural parameters and fluid dynamics
forbid the existence of 5-foot-tall
mosquitoes.

32. 2. Morphogenetic Constraints
– when organisms depart from their
normal development, they do so in only a
limited number of ways.
Example:
– If a longer limb is favorable in a given
environment, the humerus may become
elongated, but one never sees two
smaller humeri joined together in
tandem, although one could imagine the
selective advantages that such an
arrangement might have. This
observation indicates a construction
scheme that has certain rules.

33. 3. Phyletic Constraints
– historical restrictions based on the
genetics of an organism's development.
Example:
Inductive Interactions generate structure
a) Notochord is vestigial in adult vertebrae
but functional in the specification of
the neural tube
b) Pronephros of chick is the source of
uretic bud that induuces the formation
of functional kidney

34. • Canalization (Buffer systems of
development) - development appears
to be buffered so that slight
abnormalities of genotype or slight
perturbations of the environment will
not lead to the formation of abnormal
phenotypes
• Not all mutations produce mutant
phenotypes

35. • Protein that binds to a set of signal
transduction molecules that are inherently
unstable.
• Provides a way to resist fluctuation due to
slight mutation or environmental change
• Responsible for allowing mutations to
accumulate by keeping them from being
expressed until the environment changes
*transient decrease in Hsp9(damage) would
uncover pre-existing genetic interaction that
would produce morphological variations

36. Modern Synthesis
• “evolution within a species could be
explained: Diversity within a population
arose from the random production of
mutations, and the environment acted to
select the most fit phenotypes. “
• Those animals capable of reproducing
would transmit the genes that gave them
their advantage.

37. 1. Gradualism
Vs Punctuated Equilibrium
2. Extrapolation of microevolution to
macroevolution
3. Specificity of phenotype from
genotype.
*POLYPHENISM
4. Lack of genetic similarity in disparate
organisms

38. Population Genetics
Based on gene differences in adults
competing for reproductive success
Dev.Bio. And Dev.Gen
Has more concern on the “arrival” of the
fittest than the survival of the fittest.

39. 1. Evolution is caused by the inheritance of changes in
development. Modifications of embryonic or larval
development can create new phenotypes that can then be
selected.
2. Darwin's concept of "descent with modification" explained
both homologies and adaptations. The similarities of
structure were due to common ancestry (homology), while
the modifications were due to natural selection (adaptation
to the environmental circumstances).
3. The Urbilaterian ancestor can be extrapolated by looking at
the developmental genes common to invertebrates and
vertebrates and which perform similar functions. These
include the Hox genes that specify body segments, the
tinman gene that regulates heart development, the Pax6 gene
that specifies those regions able to form eyes, and the genes
that instruct head and tail formation.

40. 4. Changes in the targets of Hox genes can alter
what the Hox genes specify. The Ubx protein, for
instance, specifies halteres in flies and hindwings
in butterflies.
5. Changes of Hox gene expression within a region
can alter the structures formed by that region.
For instance, changes in the expression of Ubx
and abdA in insects regulate the production of
prolegs in the abdominal segments of the larvae.
6. Changes in Hox gene expression between body
regions can alter the structures formed by that
region. In crustaceans, different Hox expression
patterns enable the body to have or to lack
maxillipeds on its thoracic segments.

41. 7. Changes in Hox gene expression are correlated
with the limbless phenotypes in snakes.
8. Changes in Hox gene number may allow Hox
genes to take on new functions. Large changes
the numbers of Hox genes correlate with major
transitions in evolution.
9. Duplications of genes may also enable these
genes to become expressed in new places. The
formation of new cell types may result from
duplicated genes whose regulation has diverged.

42. 10. In addition to structures being homologous,
developmental pathways can be homologous. Here,
one has homologous proteins organized in homologous
ways. These pathways can be used for different
developmental phenomena in different organisms and
within the same organism.
11. Deep homology results when the homologous pathway
is utilized for the same function in greatly diverged
organisms. The instructions for forming the central
nervous system and for forming limbs are possible
examples of deep homology.
12. Modularity allows for parts of the embryo to change
without affecting other parts.
13. The dissociation of one module from another is shown
by heterochrony (changing in the timing of the
development of one region with respect to another)
and by allometry (when different parts of the organism
grow at different rates).

43. 14. Allometry can create new structures (such as the
pocket gopher cheek pouch) by crossing a threshold.
15. Duplication and divergence are important mechanisms
of evolution. On the gene level, the Hox genes, the
Distal-less genes, the MyoD genes, and many other gene
families started as single genes. The diverged members
can assume different functions.
16. Co-option (recruitment) of existing genes and pathways
for new functions is a fundamental mechanism for
creating new phenotypes. One such recruitment is the
limb development pathway being used to form eyespots
in butterfly wings.

44. 17. Developmental modules can include several tissue
types such that correlated progression occurs. here, a
change in one portion of the module causes changes in
the other portions. When skeletal bones change, the
nerves and muscles serving them also change.
18. Tissue interactions have to be conserved, and if one
component changes, the other must. If a ligand changes,
its receptor must change. Reproductive isolation may
result from changes in sperm or egg proteins.
19. Developmental constraints prevent certain phenotypes
from occurring. Such restraints may be physical (no
rotating limbs), morphogenetic (no middle finger
smaller than its neighbors), or phyletic (no neural tube
without a notochord).

45. 20. The Hsp90 protein enables cells to
accumulate genes that would otherwise give
abnormal phenotypes. When the organisms
are stressed during development, these
phenotypes can emerge.
21. The merging of the population genetics
model of evolution with the developmental
genetics model of evolution is creating a new
evolutionary synthesis that can account for
macroevolutionary as well as
microevolutionary phenomena.