Exam 3 Slide 1

1

• WHAT IS DEVELOPMENTAL BIOLOGY?
• The study of development of multicellular
  organisms
• fertilization ? embryo ? adult ? aging ? death
• Common features of development
• 1. Increase in size and cell number.
• 2. Increase in cell specialization and the
  diversity of cell types differentiation.
• 3. Pattern formation differentiated cells
  arrange themselves into organized tissues,
  organs, etc.
• 4. Development of complex morphology (shape) and
  body plan.

2

• Developmental Genetics
• Classes of genes
• 1. Housekeeping genes
• Encode proteins needed in all cells.
• For basic and essential cell functions.
• 2. Tissue-specific genes
• Give different tissues their unique features.
• 3. Toolkit genes
• Encode proteins that govern development and
  pattern formation.
• Enable cells to determine where they are, what
  they should do.

3
Vertebrate Development Frogs
Neurulation
4

• Basic Features of Vertebrate Development
• Example Amphibians (frogs)
• zygote
• ? cleavage and increase in cell number.
• blastula
• ? gastrulation and formation of germ layers
• gastrula
• ? neurulation and formation of spinal
  cord.
• neurula
• ? organogenesis and cell differentiation.
• tadpole
• ? metamorphosis change in body plan and
  lifestyle.
• frog

5
Gastrulation in the Lancet (a relative of
vertebrates)
Archenteron
Ectoderm
Ectoderm
Ectoderm
Endoderm
Endoderm
Endoderm
Blastopore
6
Frog Gastrulation
Ectoderm
Ectoderm
Animal pole
Ectoderm
Mesoderm
Archenteron
Blastocoel
Blastocoel
Endoderm
Dorsal lip
Meso- derm
Blastocoel
Dorsal lip of blastopore
Ventral lip
Yolk plug
Vegetal pole
Neural plate
Neural fold
Neural plate
7
Vertebrate Development Frogs
Neurulation
8
Neural Tube Formation (Mammals)
9
Vertebrate Development Frogs
Neurulation
10
Partial Cleavage in Birds the Blastodisc
Blastodisc
Yolk
Ectoderm
Blastocoel
Endoderm
Ectoderm
Primitive streak
Endoderm
Mesoderm
11
Development of Drosophila Eggs the Syncytial
Blastoderm
Nurse cells
Movement of maternal mRNA
Syncytial blastoderm
Nuclei line up along surface and membranes grow be
tween them
Oocyte
(a) Egg
(b) Syncytial blastoderm
12
Drosophila Development (continued)
Instars
Chitinous exoskeleton
Imaginal discs
(c) Larval instars
Pupa
Larva
(d) Imaginal discs
(f) Adult
(e) Metamorphosis
13
The Imaginal Discs of Drosophila
14
From Wolpert, L. et al. 2002 Principles of
Development. 2nd ed. New York. Oxford Univ. Press
15
Vertebrate Development Frogs
Neurulation
16
Frog Gastrulation
Ectoderm
Ectoderm
Animal pole
Ectoderm
Mesoderm
Archenteron
Blastocoel
Blastocoel
Endoderm
Dorsal lip
Meso- derm
Blastocoel
Dorsal lip of blastopore
Ventral lip
Yolk plug
Vegetal pole
Neural plate
Neural fold
Neural plate
17
Cell Fate Determination and Differentiation
Undifferentiated cells
18
Determination of the Eye Region in Tadpoles
19
Determination and Differentiation of Muscle
Cells Expression of Master Control Gene myoD
The myoD gene codes for a transcription factor
that activates transcription of other
transcription factors (including itself!) that
control expression of muscle proteins
20
Cytoplasmic Determinants in Cell Determination
and Cell Differentiation Importance of the Gray
Crescent in Amphibian Development
21
Nuclear Transplantation Technique to Determine
Nuclear Totipotency
22
Developmental Stage Determines Nuclear
Totipotency in Frogs
23
Cloning of the Sheep Dolly I
Mammary cell is extracted and grown in
nutrient- deficient solution that arrests the
cell cycle.
Nucleus containing source DNA
Electric shock opens cell membranes and
triggers cell division.
Egg cell is extracted.
Mammary cell is inserted inside covering of egg
cell.
Preparation
Cell fusion
Cell division
Nucleus is removed from egg cell with
a micropipette.
24
Cloning of the Sheep Dolly II
After a five-month pregnancy, a lamb genetically
identical to the sheep from which the
mammary cell was extracted is born.
Embryo
Embryo begins to develop in vitro.
Embryo is implanted into surrogate mother.
Development
Implantation
Birth of clone
Most cloned animals, die prematurely because of
long-term problems associated with genomic
imprinting
Dolly, 1997-2004
25
Totipotency and Stem Cells Embryonic and Adult
(Tissue-Specific) Stem Cells
26
Regulatory Control of the trp Operon A
Repressible Operon
Inactive repressor
RNA polymerase
Tryptophan absent
mRNA synthesis
Promoter
Tryptophan is synthesized
Genes are ON
Start of transcription
Operator
Tryptophan present
Tryptophan
Active repressor
RNA polymerase cannot bind
trp operon comprises protein-coding structural
genes and regulatory sequences involved in
synthesis of tryptophan
Tryptophan is not synthesized
Genes are OFF
27
The lac Operon Putting It All Together
RNA-polymerase binding site (promoter)
CAP- binding site
Lactose
Operator
Glucose
lacZ gene


Operon OFF because CAP is not bound
Repressor


Operon OFF both because lac repressor is bound
and CAP is not
RNA polymerase


CAP
Operon OFF because lac repressor is bound
RNA polymerase


CAP
mRNA synthesis

Operon ON because CAP is bound and lac repressor
is not
28
Apoptosis (Programmed Cell Death) in Development
of the Nematode Worm C. elegans
29
The Genetic Regulatory Network Controlling
Development Along the Anterior-Posterior Axis of
Drosophila
30

• Embryonic axis formation
• a. Anterior Posterior (head tail)
• b. Dorsal Ventral (back front)
• c. Left Right

31
The A P Axis in Drosophila A. Maternal effect
genes (maternal gene products) provide initial
information. B. Zygotic genes respond and
influence expression of other zygotic genes. C.
Resulting protein gradients provide positional
information to nuclei and cells. D. Results in
different patterns of transcription (and
different developmental fates) in different
regions of the embryo. E. Embryo is progressively
subdivided into smaller regions by different
patterns of gene expression and (eventually)
visible body segments.
Anterior
Posterior
32
The A P Axis in Drosophila A. Maternal effect
genes form anterior-posterior protein
gradients. B. Zygotic gap genes divide embryo
into broad regions. C. Zygotic pair-rule genes
divide embryo into stripes about two segments
wide define segment borders. D. Zygotic segment
polarity genes divide segments into anterior and
posterior halves. E. Zygotic homeotic selector
genes specify the identity of each segment.
Anterior
Posterior
33
Gradients Generated by the Maternal Effect Genes
Maternal mRNA
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34
Gradients Generated by the Maternal Effect Genes
Maternal mRNA
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35
Genetic evidence that bicoid is necessary for
development of anterior structures
36
Experimental evidence that bicoid is necessary
for development of anterior structures
37
The A P Axis in Drosophila A. Maternal effect
genes form anterior-posterior protein
gradients. B. Zygotic gap genes divide embryo
into broad regions. C. Zygotic pair-rule genes
divide embryo into stripes about two segments
wide define segment borders. D. Zygotic segment
polarity genes divide segments into anterior and
posterior halves. E. Zygotic homeotic selector
genes specify the identity of each segment.
Anterior
Posterior
38
The Zygotic Gap Genes of Drosophila

• First zygotic genes to be expressed along the A-P
  axis.
• All code for transcription factors.
• When mutant, produces embryos with major gaps in
  segmentation.

39
Phenotypic Effects of Mutation in a Gap Gene
Krüppel
Krüppel Mutant
Normal
40
Regulation of the Gap Gene Krüppel

• At low concentrations, hunchback protein
  activates Krüppel expression.
• At high concentrations, hunchback protein
  represses Krüppel expression.

41
Control of Gap Gene Expression
42
The A P Axis in Drosophila A. Maternal effect
genes form anterior-posterior protein
gradients. B. Zygotic gap genes divide embryo
into broad regions. C. Zygotic pair-rule genes
divide embryo into stripes about two segments
wide define segment borders. D. Zygotic segment
polarity genes divide segments into anterior and
posterior halves. E. Zygotic homeotic selector
genes specify the identity of each segment.
Anterior
Posterior
43
Phenotypic Effects of Mutation in a Pair-Rule
Gene ftz (fushi tarazu)
ftz Mutant Lacks Alternate Segments!
Early Embryo Area of Gene Expression
Late Embryo Area of Gene Expression
Normal Larvae Area of Gene Expression
fushi tarazu Japanese for too few segments
44
Promoter Regions of the Pair-Rule Gene
even-skipped (eve)
Stripe-specific regulatory regions!
Embryos injected with transgenes attached to a
reporter gene.
Orangeeve protein
Black reporter protein produced by transgenic
embryos
45
Specification of the Second Stripe of the
Pair-Rule Gene eve (even-skipped)
Pair-rule genes have stripe-specific regulatory
sequences with binding sites for both activators
and repressors. Activators and repressors are
transcription factors produced by both maternal
effect genes and zygotic gap genes.
46
The A P Axis in Drosophila A. Maternal effect
genes form anterior-posterior protein
gradients. B. Zygotic gap genes divide embryo
into broad regions. C. Zygotic pair-rule genes
divide embryo into stripes about two segments
wide define segment borders. D. Zygotic segment
polarity genes divide segments into anterior and
posterior halves. E. Zygotic homeotic selector
genes specify the identity of each segment.
Anterior
Posterior
47
Segment Polarity Genes

• Determine anterior posterior orientation in
  each segment.
• Activated in response to pair-rule genes.
• Intercellular signaling molecules, not
  transcription factors!
• Important after syncytial stage transcription
  factors cannot move across cell membranes!

48
The A P Axis in Drosophila A. Maternal affect
genes form anterior-posterior protein
gradients. B. Zygotic gap genes divide embryo
into broad regions. C. Zygotic pair-rule genes
divide embryo into stripes about two segments
wide define segment borders. D. Zygotic segment
polarity genes divide segments into anterior and
posterior halves. E. Zygotic homeotic selector
genes specify the identity of each segment.
Anterior
Posterior
49
Homeotic Mutants in Drosophila
Homeotic normal body parts in wrong location
haltere
Normal fly
bithorax mutant (wings instead of halteres)
antennapedia mutant (legs instead of antennae)
50
The Homeotic Selector Genes in Drosophila
Several related genes, organized into two
complexes Antennapedia and Bithorax

• Combinatorial expression patterns determine
  segment identity.
• All adjacent on same chromosome.
• Anterior posterior expression pattern
  corresponds to position on chromosome (!)
• All are transcription factors that contain a
  particular DNA-binding domain the homeobox or
  homeodomain.

51
The Homeodomain of Homeotic Selector Genes
2
Homeodomain
3
COOH
1
NH2
Variable region
All homeotic selector genes code for
transcription factors that contain a
60-amino-acid sequence common to all the
homeodomain
DNA
52
Evolutionary conservation of homeobox (Hox) genes
abd-A
abd-B
Ubx
lab
Scr
pb
Antp
Dfd
Fruit fly embryo
Fruit fly

• Found in virtually all multicellular animals.
• Conserved DNA sequence and gene arrangement.
• Duplications of genes or complexes common in
  vertebrates.
• Often functionally similar (e.g. mouse Hox gene
  works in fruit flies).

Hox 1
Hox 2
Hox 3
Hox 4
Mouse embryo
Mouse
53

• Embryonic axis formation
• a. Anterior Posterior (head tail)
• b. Dorsal Ventral (back front)
• c. Left Right

54
The Dorsal-Ventral Axis in Drosophila
Maternal effect gene pipe codes for enzyme that
leads to production of extracellular signal
protein spätzle on ventral surface of egg.
55
Spätzle causes nuclear localization of the
maternal protein dorsal on the ventral surface of
the egg.
56
The Gradient of Intranuclear Dorsal Protein
The protein dorsal is a transcription factor that
stimulates the development of ventral structures.
Huh? How the heck did it get the name dorsal???
57

• Zygotic genes respond to ventral-to-dorsal
  gradient of nuclear dorsal protein in a variety
  ways for example
• snail (sna) promoter weakly activated by
  dorsal expressed only in extreme ventral region
  of embryo.
• rhomboid (rho) promoter strongly activated by
  dorsal, but repressed by snail expressed
  ventrolaterally.
• zerknüllt (zen) promoter strongly repressed by
  dorsal expressed only in extreme dorsal region
  of embryo.
• decapentaplegic (dpp) promoter weakly repressed
  by dorsal expressed in dorsal and dorsolateral
  regions.

58
Gene Expression Along the Dorsal-Ventral Axis
59
Embryonic Axis Formation in DrosophilaSummary

• Maternal genes products (mRNAs and proteins) are
  distributed unequally in the egg and provide
  initial positional information.
• Maternal gene products initiate a complex cascade
  of zygotic gene activity, leading to the
  production of a suite of transcription factors
  and (during later stages) intercellular signaling
  molecules that provide more detailed positional
  information.

60
Intercellular Signaling and Signal Transduction
Pathways

• How do chemical signals in the extracellular
  environment lead to differential gene expression
  within a cell?
• Signal transduction pathways!

61
Four Types of Cell-Cell Signaling
Secretory cell
Gap junction
Adjacent target cells
Direct contact
Paracrine signaling
Hormone secretion into blood by endocrine gland
Neurotransmitter
Targetcell
Nerve cell
Blood vessel
Synaptic gap
Distant target cells
Synaptic signaling
Endocrine signaling
62
Extracellular Signal
Cell Membrane
Trans-membrane Receptor

Extracellular Signals and the Intracellular
Signaling Cascade
Signal Cascade
Modulation by other factors
Amplification
Regulation of Metabolism
Altered Gene Expression
Changes in Cell Shape
63
Cell Specificity in Signaling

• Different cells may respond differently to the
  same signal molecule!
• Response depends on the specific receptor
  proteins and relay proteins that a cell possesses.

64
Tyrosine Kinase Receptor Inactive
65
Receptor Tyrosine Kinase Active I
When signal molecules attach to the binding site,
the two receptor proteins aggregate, forming a
dimer
Using phosphate groups from ATP, the tyrosine
kinase region of each polypeptide chain
phosphorylates the other!
66
Receptor Tyrosine Kinase Active II
Intracellular relay proteins bind to
phosophorylated tyrosines and are themselves
activated!
Each activated relay protein initiates a signal
transduction cascade!
67
G-Protein-Linked Receptors Structure
68
G-Protein-Linked Receptors Inactive Form
69
G-Protein-Linked Receptors Activated!
Activated enzyme initiates a signal transduction
cascade!
70
G-Protein-Linked Receptors Return to Inactive
Form
71
Phosphorylation and Dephosphorylation by Protein
Kinases and Protein Phosphatases in Signal
Cascades
Kinase activates
Signal in
Inactive signal molecule
Active signal molecule
Signal out
Phosphatase inactivates!
72
How Extracellular Signals and Signal Transduction
Alter Gene Regulation
73
Embryonic Induction and Intercellular Signaling

• Induction change or restriction of
  developmental fate of cells due to signals
  received from neighboring cells.
• Examples
• Induction of the notochord by the dorsal lip of
  amphibian embryos.
• Induction of the vertebrate eye.

74
Spemann and Mangolds Dorsal Lip Transplant
Experiment (1924)
Discard mesoderm opposite dorsal lip
Dorsal lip cells cause ectodermal cells to form
neural tube via induction
Dorsal lip
Donor mesoderm from dorsal lip of another frog
embryo
Primary neural fold
Primary notochord and neural development
Secondary notochord and neural development
Secondary neural development
75
Development of the Vertebrate Eye Lens by
Induction
Epidermis
Optic cup
Wall of forebrain
Lens
Lens vesicle
Lens
Sen- sory layer
Neural cavity
Optic nerve
Retina
Pigment layer
Optic stalk
Lens invagination
Transplant experiments demonstrate that growing
optic stalk causes overlying epidermal cells to
develop into lens tissue via induction
76
Embryonic Induction and Morphogens

• Morphogen a diffusible signal that provides
  concentration-dependent positional information.
• Morphogens often produced by organizer cells that
  convey positional information.
• Target cells interpret signal differently
  depending on concentration (similar to what we
  have seen in development of Drosophila embryos).

77
Organizers and a Morphogen Gradient
Concentration of morphogen
Organizer cells secreting morphogen
Organ A
Organ B
Organ C
Distance from secretion site
Embryo
Decreasing morphogen concentration gradient
78
The Morphogen Activin in Frog Embryos
Develops into notochord
Secretion of morphogen activin
Animal pole
Develops into muscle
Develops into epidermis
Vegetal pole
79
Two Types of Inductive Signals
Contact-dependent Signals
Diffusible Signals
Receptor
Signal
Note Receiving cells can be distant!
80
Contact-Dependent Notch Signaling

• Delta transmembrane signal.
• Notch transmembrane receptor.
• When bound to Delta, Notch cytoplasmic domain
  cleaved by protease, enters nucleus to act as
  transcription factor.
• LIN-12 (C. elegans) Notch (D. melanogaster)

CSL transcription factor
81
Contact-Dependent Notch Signaling and Cell Fate
in Neurogenic Ectoderm of Drosophila

• In Drosophila, undifferentiated neurogenic
  ectodermal cells have two potential fates
• Neuroblasts (nerve cells) about 25 adopt this
  fate.
• Epidermal cells about 75 adopt this fate.
• Cells differentiate in a regular lattice-like
  pattern How?
• Lateral inhibition via Notch signaling!

UndifferentiatedNeurogenic Ectoderm
Neuroblasts Epidermal Cells
82
Lateral Inhibition via Notch Signaling
Delta
Notch

• Initially more-or-less equivalent cells with both
  signals and receptors.
• Slight initial variations among cells reinforced
  by positive feedback loop one cell becomes a
  signaler (neuroblast), surrounding cells become
  receivers (epidermal cells).
• Lateral inhibition results in two stable
  populations of cells!

Neuroblast
Epidermal Cell
83
Lateral Inhibition of Neural Cell Development via
Contact-Dependent Notch Signaling The Molecular
Details
bHLH proteins basic Helix-Loop-Helix
transcription factors Stimulate neuronal
differentiation
Initially equivalent neugenic ectodermal cells
Neuroblast
Delta
Notch
Epidermal cell
Initially equivalent neugenic ectodermal cells
84
Two Types of Inductive Signals
Contact-dependent Signals
Diffusible Signals
Receptor
Signal
Note Receiving cells can be distant!
85
Development of the Nematode Worm C. elegans
Egg
Egg and sperm line
Pharynx
Intestine
Nervous system
(a)
Vulva
Gonad
Cuticle- Making cells
Nervous system
Intestine
Pharynx
Cuticle
Egg
Vulva
Sperm
Gonad
(b)
Adult nematode
86
Cell Signaling and Induction in the Development
of the Nematode Vulva
87
Development of the Nematode Vulva

• Three types of cells involved
• Six Vulval Precursor Cells (VPCs) all initially
  competent to form vulva, but usually only 3 do
  so the other 3 usually become epidermal cells.
• Anchor cell sits above VPCs and produces
  diffusible inductive signal necessary for vulva
  formation.
• Epidermal cells inhibit vulval differentiation
  in VPCs unless signal from anchor cell is
  received.

Anchor cell
VPCs
88
The Nematode Vulva Diffusible Signaling
Dose-dependent response to signal from anchor
cell! VPC closest to anchor cell gets highest
dose, becomes primary (1º) VPC. Adjacent two
VPCs receive intermediate dose, become secondary
(2º) VPCs. Three other VPCs (two shown) become
epidermal cells.
Diffusible signal protein is LIN-3 an Epidermal
Growth Factor (EGF)
89
Development of the Nematode VulvaNormal Cell
Fate
Outer vulva
Outer vulva
Inner vulva
90
The Importance of the Anchor Cell Signal
Experimental Evidence

• Destruction of anchor cell
• No vulval development! All VPCs take on
  epidermal fate.
• Mutations in genes for either LIN-3 (signal) or
  LET-23 (receptor)
• No vulval development! All VPCs take on
  epidermal fate.

91
Molecular Details of the Inductive Signal

• Anchor cell produces diffusible extracellular
  signal protein (LIN-3), an epidermal growth
  factor.
• LIN-3 activates membrane receptor protein
  (LET-23), a receptor tyrosine kinase.
• Activated LET-23 interacts with an adapter
  protein (SEM-5) to activate Ras (LET-60), a
  GTP/GDP binding protein.
• Activated GTP form of Ras in turn activates Raf
  (LIN-45), a serine / threonine kinase.
• Activated Raf inhibits the action of LIN-1, a
  transcription factor that normally represses
  transcription of vulval differentiation genes.

92
The Nematode Vulva Contact-Dependent Signaling
Diffusible EGF signaling from anchor cell
activates lateral contact-dependent LIN-12 /
Notch signaling from 1º VPC to 2º VPCs. LIN-12
signals received from 1º VPC by 2º VPCs activate
pathways necessary for 2º development, which in
turn repress 1º pathways activated by EGF
signaling.
93
Development of the Nematode VulvaSummary of
Cell-Cell Interactions
94
Components of Vertebrate Limbs
Distal
Proximal
Distal
Proximal
Mouse
Chicken
95
Axes of Development of Vertebrate Limbs
Forelimb (right wing) of birds
96
Development of Vertebrate Limbs

• Development begins as limb buds with two
  components
• Ectoderm
• surface layer of cells.
• eventually gives rise to skin, hair, feathers,
  etc.
• Includes apical ectodermal ridge along
  anteriorposterior axis, separating bud into
  dorsal and ventral sides.
• Mesoderm
• underlies ectoderm.
• eventually gives rise to bone, cartilage, muscle,
  tendon.

Chick embryo with limb buds
97
Important Regions of the Developing Limb
Apical Ectodermal Ridge (AER) secretes
Fibroblast Growth Factor (FGF). Zone of
Polarizing Activity (ZPA) or Polarizing Region
region near proximal posterior margin of early
limb bud that secretes Sonic Hedgehog
(SHH) Progress Zone Zone of mesodermal cells
that underlie the AER.
Time
98
Proximal Distal Limb Development The Role of
the AER and FGF in Chick Embryos I
Experiment 1 Remove AER of limb buds. Result
Proximaldistal development ends prematurely,
only proximal elements form.
Conclusion The AER is necessary to promote
normal proximaldistal limb elongation.
99
Proximal Distal Limb Development The Role of
the AER and FGF in Chick Embryos II
Experiment 2 Remove AER but replace it with a
bead soaked in FGF. Result Normal (or nearly
normal) proximal distal development.
Conclusion FGF is the signal molecule that
promotes proximal-distal limb elongation. FGF
binds to FGF receptors in mesodermal cells of
progress zone, activating a tyrosine kinase
pathway similar to that of nematode VPCs.
100
Proximal Distal Limb Development The Role of
the AER and FGF in Chick Embryos III
Experiment 3 Remove AER from wing bud, replace
with AER from leg bud. Result Normal wing
development. Experiment 4 Remove progress zone
mesoderm from a wing bud and replace it with leg
bud mesoderm. Result Distal limb develops as
leg, not wing!
Conclusions 1. AER and FGF are necessary for
growth but not limb identity. 2. Limb identity
specified by underlying mesodermal cells of the
progress zone.
101
Timing of AER Removal Is Important
102
Two Models of ProximalDistal Patterning in Limbs
Progress zone model P-D fate not prespecified,
determined by time in progress zone
Prespecification model P-D pattern controlled by
selective growth of predetermined cells
How the two models explain results of removal of
AER
103
Anterior Posterior Limb Development The Role
of the ZPA and SHH in Chick Embryos I
Experiment 1 Transplant posterior limb bud
(including ZPA) from one chick to anterior limb
bud of a second chick embryo. Experiment 2
Implant a bead soaked with SHH in anterior region
of limb bud. Result Mirror-image duplication of
posterior structures (digits) in a dose-dependent
fashion!
Zone of Polarizing Activity (ZPA), secretes sonic
hedgehog (SHH)
104
Anterior Posterior Limb Development The Role
of the ZPA and SHH in Chick Embryos II
SHH acts as a morphogen produces dose-dependent
effects
105
Dorsal Ventral Limb Development The Role of
Dorsal Ectoderm and WNT-7a
Dorsal ectoderm secretes WNT-7a, a protein
similar to wingless of Drosophila.
WNT-7a loss-of-function mutants no dorsal limb
structures! Expression of WNT-7a on ventral
ectoderm no ventral limb structures!
106
Hox Gene Expression During Limb Development

• Nested expression along P-D and A-P axis.
• Expression pattern mirrors gene arrangement on
  chromosome.
• Have we seen this before?
• YES, homeotic/hox gene control of development
  along the A-P body axis in Drosophila and other
  animals!

Hoxa genes nested P-D expression
Hoxd genes nested A-P expression
107
Summary Development of Vertebrate Limbs

• Three axes of limb development
• Proximal-distal axis regulated primarily by
  Fibroblast Growth Factors (FGF) produced by
  Apical Ectodermal Ridge (AER).
• Anterior-posterior axis regulated primarily by
  Sonic Hedgehog (SHH) produced by Zone of
  Polarizing Activity (ZPA).
• Dorsal-ventral axis regulated primarily by
  WNT-7a produced by Dorsal Ectoderm.
• Nested expression of Hox genes provides
  fine-tuned positional information and precise
  control of limb patterning.