Chapter 29
Gradients,cascades,
and signaling pathways
29.1 Introduction
29.2 Fly development uses a cascade of transcription factors
29.3 A gradient must be converted into discrete compartments
29.4 Maternal gene products establish gradients in early embryogenesis
29.5 Anterior development uses localized gene regulators
29.6 Posterior development uses another localized regulator
29.7 How are mRNAs and proteins transported and localized?
29.8 Dorsal-ventral development uses localized receptor-ligand interactions
29.9 TGFb/BMPs are diffusible morphogens
29.10 Cell fate is determined by compartments that form by the blastoderm stage
29.11 The wingless/wnt signaling pathway
29.12 Complex loci are extremely large and involved in regulation
29.13 The homeobox is a common coding motif in homeotic genes
Development begins with a single fertilized egg,but gives rise to
cells that have different developmental fates,The problem of early
development is to understand how this asymmetry is introduced,
how does a single initial cell give rise within a few cell divisions to
progeny cells that have different properties from one another? The
means by which asymmetry is generated varies with the type of
organism,The egg itself may be homogeneous,with the acquisition
of asymmetry depending on the process of the initial division cycles,
as in the case of mammals,Or the egg may have an initial
asymmetry in the distribution of its cytoplasmic components,which
in turn gives rise to further differences as development proceeds,as
in the case of Drosophila
29.1 Introduction
Development begins with a single fertilized egg,but gives rise to
cells that have different developmental fates,The problem of early
development is to understand how this asymmetry is introduced,
how does a single initial cell give rise within a few cell divisions to
progeny cells that have different properties from one another? The
means by which asymmetry is generated varies with the type of
organism,The egg itself may be homogeneous,with the acquisition
of asymmetry depending on the process of the initial division cycles,
as in the case of mammals,Or the egg may have an initial
asymmetry in the distribution of its cytoplasmic components,which
in turn gives rise to further differences as development proceeds,as
in the case of Drosophila
29.1 Introduction
Homeotic genes are defined by
mutations that convert one body part
into another; for example,an insect leg
may replace an antenna.
Segmentation genes are concerned with
controlling the number or polarity of
body segments in insects.
29.2 Fly development uses a cascade of
transcription factors
Figure 29.1 Gradients in the
egg are translated into
segments on the anterior-
posterior axis and into
specialized structures on the
dorsal-ventral axis of the
larva,and then into the
segmented structure of the
adult fly.
29.3 A gradient must be
converted into discrete
compartments
Figure 29.2 The early
development of the
Drosophila egg occurs in a
common cytoplasm until the
stage of cellular blastoderm.
29.3 A gradient must be
converted into discrete
compartments
Morphogen is a factor that
induces development of
particular cell types in a manner
that depends on its concentration.
29.4 Maternal gene products establish
gradients in early embryogenesis
Figure 29.3 A Drosophila follicle contains an outer surface of
follicle cells that surround nurse cells that are in close contact
with the oocyte,Nurse cells are connected by cytoplasmic bridges
to each other and to the anterior end of the oocyte,Follicle cells
are somatic; nurse cells and the oocyte are germline in origin.
29.4 Maternal gene products establish
gradients in early embryogenesis
Figure 29.4 Each of the four maternal systems that functions in the egg is initiated
outside the egg,The pathway is carried into the egg,where each pathway has a
localized product that is the morphogen,This may be a receptor or a regulator of
gene expression,The final component is a transcription factor,which acts on
zygotic targets that are responsible for the next stage of development.
29.4 Maternal gene products establish
gradients in early embryogenesis
Figure 29.5 Translation
of a localized mRNA
generates a gradient of
protein as the products
diffuses away from the
site of synthesis.
29.5 Anterior
development uses
localized gene regulators
Figure 29.6 Mutant embryos that
cannot develop can be rescued by
injecting cytoplasm taken from a
wild-type embryo,The donor can
be tested for time of appearance and
location of the rescuing activity; the
recipient can be tested for time at
which it is susceptible to rescue and
the effects of injecting material at
different locations.
29.5 Anterior
development uses
localized gene regulators
Figure 29.7 Bicoid protein
forms a gradient during D,
melanogaster development
that extends for ~200 mm
along the egg of 500 mm.
29.5 Anterior
development uses
localized gene regulators
Figure 29.7 Bicoid protein
forms a gradient during D,
melanogaster development
that extends for ~200 mm
along the egg of 500 mm.
29.5 Anterior
development uses
localized gene regulators
Figure 29.17 In each axis-determining system,localized
products in the egg cause other maternal RNAs or proteins
to be broadly localized at syncytial blastoderm,and zygotic
RNAs are transcribed in bands at cellular blastoderm.
29.5 Anterior development uses
localized gene regulators
Figure 29.8 The
posterior pathway
has two branches,
responsible for
abdominal
development and
germ cell formation.
29.6 Posterior development uses
another localized regulator
Figure 29.2 The early
development of the
Drosophila egg occurs in a
common cytoplasm until the
stage of cellular blastoderm.
29.6 Posterior
development uses
another localized
regulator
Figure 29.6 Mutant embryos that
cannot develop can be rescued by
injecting cytoplasm taken from a
wild-type embryo,The donor can
be tested for time of appearance
and location of the rescuing
activity; the recipient can be
tested for time at which it is
susceptible to rescue and the
effects of injecting material at
different locations.
29.6 Posterior
development uses another
localized regulator
Figure 29.9 nanos products are
localized at the posterior end of a
Drosophila embryo,The upper
photograph shows the tightly
localized RNA inthe very early
embryo (at the time of the 3rd
nuclear division),The lower
photograph shows the spreadingof
nanos protein at the 8th nuclear
division,Photographs kindly
provided by Ruth Lehmann.
29.6 Posterior
development uses another
localized regulator
Figure 29.10 Some mRNAs are
transported into the Drosophila
egg as ribonucleoprotein
particles,They move to their
final sites of localization by
association with tracks that may
be either either microtubules or
actin filaments.
29.7 How are mRNAs and
proteins transported and
localized?
Figure 29.11 Dorsal and ventral
identities are first distinguished
when grk mRNA is localized
on the dorsal side of the oocyte,
Synthesis of Grk activates the
receptor coded by torpedo,
which triggers a MAPK
pathway in the follicle cells.
29.8 Dorsal-ventral
development uses
localized receptor-
ligand interactions
Figure 29.4 Each of the four maternal systems that functions in the egg is initiated
outside the egg,The pathway is carried into the egg,where each pathway has a
localized product that is the morphogen,This may be a receptor or a regulator of
gene expression,The final component is a transcription factor,which acts on
zygotic targets that are responsible for the next stage of development.
29.8 Dorsal-ventral development uses
localized receptor-ligand interactions
Figure 29.12 Wild-type Drosophila
embryos have distinct dorsal and
ventral structures,Mutations in
genes of the dorsal group prevent the
appearance of ventral structures,and
the ventral side of the embryo is
dorsalized,Ventral structures can be
restored by injecting cytoplasm
containing the Toll gene product.
29.8 Dorsal-ventral
development uses
localized receptor-
ligand interactions
Figure 29.13 The dorsal-ventral
pathway is summarized on the right
and shown in detail on the left,It
involves interactions between
follicle cells and the oocyte,The
pathway moves into the oocyte
when spatzle binds to Toll and
activates the morphogen,The
pathway is completed by
transporting the transcription factor
dorsal into the nucleus.
29.8 Dorsal-ventral
development uses
localized receptor-
ligand interactions
Figure 29.14 Activation of IL1
receptor triggers formation of a
complex containing adaptor(s) and
a kinase,The IRAK kinase
activates NIK,which
phosphorylates I-kB,This triggers
degradation of I-kB,releasing NF-
kB,which translocates to the
nucleus to activate transcription.
29.8 Dorsal-ventral
development uses
localized receptor-
ligand interactions
Figure 21.2 The activity of a
regulatory transcription factor
may be controlled by synthesis
of protein,covalent
modification of protein,ligand
binding,or binding of
inhibitors that sequester the
protein or affect its ability to
bind to DNA.
29.8 Dorsal-ventral
development uses
localized receptor-
ligand interactions
Figure 29.15 Dorsal protein forms a
gradient of nuclear localization from
ventral to dorsal side of the embryo,On the
ventral side (lower) the protein identifies
bright nuclei; on the dorsal side (upper) the
nuclei lack proteDorsal protein forms a
gradient of nuclear localization from
ventral to dorsal side of the embryo,On the
ventral side (lower) the protein identifies
bright nuclei; on the dorsal side (upper) the
nuclei lack protein and show as dark holes
in the bright cytoplasm,
29.8 Dorsal-ventral
development uses
localized receptor-
ligand interactions
Figure 29.16
Dorsal-ventral
patterning
requires the
successive
actions of
three localized
systems.
29.8 Dorsal-ventral development uses
localized receptor-ligand interactions
Figure 29.17 In each axis-determining system,localized
products in the egg cause other maternal RNAs or proteins
to be broadly localized at syncytial blastoderm,and zygotic
RNAs are transcribed in bands at cellular blastoderm.
29.8 Dorsal-ventral development uses
localized receptor-ligand interactions
Figure 26.35 Activation
of TGFb receptors
causes phosphorylation
of a Smad,which is
imported into the
nucleus to activate
transcription.
29.9 TGF/BMPs are diffusible morphogens
Figure 29.18
The morphogen
dpp forms a
gradient
originating on
the dorsal side
of the fly
embryo,This
prevents the
formation of
neural
structures and
induces
mesenchymal
structures.
29.9 TGF/BMPs are diffusible morphogens
Figure 29.19 Two
common pathways
are used in early
development of
Xenopus,The
Niewkoop center
uses the Wnt
pathway to induce
the Spemann
organizer,The
organizer diffuses
dorsalizing factors
that counteract the
effects of the
ventralizing BMPs.
29.9 TGF/BMPs are diffusible morphogens
Figure 29.20 The TGFb/Bmp
signaling pathway is conserved in
evolution,The ligand may be
sequestered by an antagonist,which
is cleaved by a protease,Ligand
binds to a dimeric receptor,causing
the phosphorylation of a specific
Smad,which together with a Co-
Smad translocates to the nucleus,to
activate gene expression.
29.9 TGF/BMPs are
diffusible morphogens
Gap in DNA is the absence
of one or more nucleotides
in one strand of the duplex.
29.10 Cell fate is determined by compartments
that form by the blastoderm stage
Figure 29.21 Drosophila
development proceeds through
formation of compartments
that define parasegments and
segments.
29.10 Cell fate is
determined by
compartments that form by
the blastoderm stage
Figure 29.22
Segmentation genes affect
the number of segments
and fall into three groups.
29.10 Cell fate is
determined by
compartments that form
by the blastoderm stage
Figure 29.23
Maternal and
segmentation genes
act progressively on
smaller regions of
the embryo.
29.10 Cell fate is
determined by
compartments that form
by the blastoderm stage
Figure 29.24 Expression of the
gap genes defines adjacent
regions of the embryo,The gap
genes control the pair-rule
genes,each of which is
expressed in 7 stripes.
29.10 Cell fate is
determined by
compartments that form
by the blastoderm stage
Figure 29.25 ftz
mutants have half the
number of segments
present in wild-type,
Photographs kindly
provided by Walter
Gehring.
29.10 Cell fate is determined by compartments
that form by the blastoderm stage
Figure 29.26 Transcripts of the ftz gene are localized in stripes
corresponding to even numbered parasegments,The expressed regions
correspond to the regions that are missing in the ftz mutant of the
previous figure,Photograph kindly provided by Walter Gehring.
29.10 Cell fate is determined by compartments
that form by the blastoderm stage
Figure 29.27 The eve stripe in
parasegment 3 is activated by
hunchback and bicoid,Repression
by giant sets the anterior boundary;
repression by Kruppel sets the
posterior boundary,Mulltiple
binding sites for these proteins in a
480 bp region of the promoter
control expression of the gene.
29.10 Cell fate is
determined by
compartments that form
by the blastoderm stage
Figure 29.28 Simultaneous staining
for ftz (brown) and eve (grey)
shows that they are first expressed
as broad alternating stripes at the
time of blastoderm (upper),but
narrow during the next 1 hour of
development (lower),Photographs
kindly provided by Peter Lawrence.
29.10 Cell fate is
determined by
compartments that form
by the blastoderm stage
Figure 29.29 Engrailed protein is localized in nuclei and
forms stripes as precisely delineated as 1 cell in width,
Photograph kindly provided by Patrick O'Farrell.
29.10 Cell fate is determined by compartments
that form by the blastoderm stage
Figure 29.30 Reciprocal interactions maintain Wg and Hg signaling between adjacent
cells,Wg activates a receptor,which activates a pathway leading to translocation of
Arm to the nucleus,This leads to expression of Hedgehog protein,which is secreted
to act on the neighboring cell,where it maintains Wg expression.
29.11 The wingless/wnt signaling pathway
Figure 29.31 Wg secretion is assisted by
porc,Wg activates the Dfz2 receptor,
which inhibits Zw3 kinase,Active Zw3
causes turnover of Arm,Inhibition of
Zw3 stabilizes Arm,allowing it to
translocate to the nucleus,In the nucleus,
Arm partners Pan,and activates target
genes (including engrailed),A similar
pathway is found in vertebrate cells
(components named in blue).
29.11 The wingless/wnt
signaling pathway
Figure 29.19 Two common pathways are used in early development of Xenopus,The
Niewkoop center uses the Wnt pathway to induce the Spemann organizer,The organizer
diffuses dorsalizing factors that counteract the effects of the ventralizing BMPs.
29.11 The wingless/wnt signaling pathway
Homeotic genes are defined by
mutations that convert one body
part into another; for example,an
insect leg may replace an antenna.
29.12 Complex loci are extremely
large and involved in regulation
Figure 29.32 The homeotic
genes of the ANT-C complex
confer identity on the most
anterior segments of the fly,
The genes vary in size,and
are interspersed with other
genes,The antp gene is very
large and has alternative
forms of expression.
29.12 Complex loci are
extremely large and
involved in regulation
Figure 29.33 A four-winged fly is produced by a triple mutation in abx,bx,
and pbx at the BX-C complex,Photograph kindly provided by Ed Lewis.
29.12 Complex loci are extremely
large and involved in regulation
Figure 29.34 The bithorax (BX-
C) locus has 3 coding units,A
series of regulatory mutations
affects successive segments of
the fly,The sites of the
regulatory mutations show the
regions within which deletions,
insertions,and translocations
confer a given phenotype.
29.12 Complex loci are
extremely large and
involved in regulation
Figure 29.34 The bithorax (BX-
C) locus has 3 coding units,A
series of regulatory mutations
affects successive segments of
the fly,The sites of the
regulatory mutations show the
regions within which deletions,
insertions,and translocations
confer a given phenotype.
29.12 Complex loci are
extremely large and
involved in regulation
Figure 29.34 The bithorax (BX-
C) locus has 3 coding units,A
series of regulatory mutations
affects successive segments of
the fly,The sites of the
regulatory mutations show the
regions within which deletions,
insertions,and translocations
confer a given phenotype.
29.12 Complex loci are
extremely large and
involved in regulation
Homeobox describes the conserved sequence
that is part of the coding region of D,
melanogaster homeotic genes; it is also found
in amphibian and mammalian genes expressed
in early embryonic development.
Paralogs are highly similar proteins that are
coded by the same genome.
29.13 The homeobox is a common
coding motif in homeotic genes
Figure 21.3 Transcription factor SP1 has a series of three
zinc fingers,each with a characteristic pattern of cysteine
and histidine residues that constitute the zinc-binding site.
29.13 The homeobox is a common coding
motif in homeotic genes
Figure 21.11 The homeodomain of the Antennapedia gene represents the major
group of genes containing homeoboxes in Drosophila; engrailed (en) represents
another type of homeotic gene; and the mammalian factor Oct-2 represents a
distantly related group of transcription factors,The homeodomain is
conventionally numbered from 1 to 60,It starts with the N-terminal arm,and
the three helical regions occupy residues 10-22,28-38,and 42-58.
29.13 The homeobox is a common coding
motif in homeotic genes
Figure 21.9 TR and RAR bind the
SMRT corepressor in the absence
of ligand,The promoter is not
expressed,When SMRT is
displaced by binding of ligand,
the receptor binds a coactivator
complex,This leads to activation
of transcription by the basal
apparatus.
29.13 The homeobox is
a common coding motif
in homeotic genes
Figure 21.10 The
homeodomain may be the
sole DNA-binding motif in
a transcriptional regulator
or may be combined with
other motifs,It represents a
discrete (60 residue) part of
the protein.
29.13 The homeobox is a common coding
motif in homeotic genes
Figure 29.35 Mouse and human
genomes each contain 4 clusters of
genes that have homeoboxes,The
order of genes reflects the regions in
which they are expressed on the
anterior-posterior axis,The Hox genes
are aligned with the fly genes
according to homology,which is
strong for groups 1,2,4,and 9,The
genes are named according to the
group and the cluster,e.g.,HoxA1 is
the most anterior gene in the HoxA
group,All Hox genes are present in
both man and mice except for some
mouse genes missing from cluster C
(indicated by half boxes).
29.13 The homeobox is a common coding
motif in homeotic genes
Figure 29.36 A comparison of ANT-
C/BX-C and HoxB expression patterns
shows that the individual gene products
share a progressive localization of
expression towards the more posterior
of the animal proceeding along the
gene cluster from left to right,
Expression patterns show the regions
of transcription in the fly epidermis at
10 hours,and in the central nervous
system of the mouse embryo at 12 days.
29.13 The homeobox is a
common coding motif in
homeotic genes
Figure 29.36 A comparison of ANT-
C/BX-C and HoxB expression patterns
shows that the individual gene products
share a progressive localization of
expression towards the more posterior
of the animal proceeding along the
gene cluster from left to right,
Expression patterns show the regions
of transcription in the fly epidermis at
10 hours,and in the central nervous
system of the mouse embryo at 12 days.
29.13 The homeobox is a
common coding motif in
homeotic genes
1,The development of segments in Drosophila occurs by
the actions of segmentation genes that delineate
successively smaller regions of the embryo,
2,Each of the 4 maternal systems consists of a cascade
which generates a locally distributed or locally active
morphogen.
3,The major anterior-posterior axis is determined by two
systems,the anterior system establishes a gradient of bicoid
from the anterior pole; and the posterior system produces
nanos protein in the posterior half of the egg.
4,The early embryo consists of a syncytium,in which
nuclei are exposed to common cytoplasm.
29.14 Summary
5,Three gap genes are zinc-finger proteins,and one is a
basic zipper protein,
6,Homeotic genes impose the program that determines
the unique differentiation of each segment,
7,The genes of the ANT-C and BX-C loci,and many
segmentation genes (including the maternal gene bicoid
and most of the pair-rule genes) contain a conserved
motif,the homeobox,
8,Drosophila genes containing homeoboxes form an
intricate regulatory network,in which one gene may
activate or repress another.
29.14 Summary
Gradients,cascades,
and signaling pathways
29.1 Introduction
29.2 Fly development uses a cascade of transcription factors
29.3 A gradient must be converted into discrete compartments
29.4 Maternal gene products establish gradients in early embryogenesis
29.5 Anterior development uses localized gene regulators
29.6 Posterior development uses another localized regulator
29.7 How are mRNAs and proteins transported and localized?
29.8 Dorsal-ventral development uses localized receptor-ligand interactions
29.9 TGFb/BMPs are diffusible morphogens
29.10 Cell fate is determined by compartments that form by the blastoderm stage
29.11 The wingless/wnt signaling pathway
29.12 Complex loci are extremely large and involved in regulation
29.13 The homeobox is a common coding motif in homeotic genes
Development begins with a single fertilized egg,but gives rise to
cells that have different developmental fates,The problem of early
development is to understand how this asymmetry is introduced,
how does a single initial cell give rise within a few cell divisions to
progeny cells that have different properties from one another? The
means by which asymmetry is generated varies with the type of
organism,The egg itself may be homogeneous,with the acquisition
of asymmetry depending on the process of the initial division cycles,
as in the case of mammals,Or the egg may have an initial
asymmetry in the distribution of its cytoplasmic components,which
in turn gives rise to further differences as development proceeds,as
in the case of Drosophila
29.1 Introduction
Development begins with a single fertilized egg,but gives rise to
cells that have different developmental fates,The problem of early
development is to understand how this asymmetry is introduced,
how does a single initial cell give rise within a few cell divisions to
progeny cells that have different properties from one another? The
means by which asymmetry is generated varies with the type of
organism,The egg itself may be homogeneous,with the acquisition
of asymmetry depending on the process of the initial division cycles,
as in the case of mammals,Or the egg may have an initial
asymmetry in the distribution of its cytoplasmic components,which
in turn gives rise to further differences as development proceeds,as
in the case of Drosophila
29.1 Introduction
Homeotic genes are defined by
mutations that convert one body part
into another; for example,an insect leg
may replace an antenna.
Segmentation genes are concerned with
controlling the number or polarity of
body segments in insects.
29.2 Fly development uses a cascade of
transcription factors
Figure 29.1 Gradients in the
egg are translated into
segments on the anterior-
posterior axis and into
specialized structures on the
dorsal-ventral axis of the
larva,and then into the
segmented structure of the
adult fly.
29.3 A gradient must be
converted into discrete
compartments
Figure 29.2 The early
development of the
Drosophila egg occurs in a
common cytoplasm until the
stage of cellular blastoderm.
29.3 A gradient must be
converted into discrete
compartments
Morphogen is a factor that
induces development of
particular cell types in a manner
that depends on its concentration.
29.4 Maternal gene products establish
gradients in early embryogenesis
Figure 29.3 A Drosophila follicle contains an outer surface of
follicle cells that surround nurse cells that are in close contact
with the oocyte,Nurse cells are connected by cytoplasmic bridges
to each other and to the anterior end of the oocyte,Follicle cells
are somatic; nurse cells and the oocyte are germline in origin.
29.4 Maternal gene products establish
gradients in early embryogenesis
Figure 29.4 Each of the four maternal systems that functions in the egg is initiated
outside the egg,The pathway is carried into the egg,where each pathway has a
localized product that is the morphogen,This may be a receptor or a regulator of
gene expression,The final component is a transcription factor,which acts on
zygotic targets that are responsible for the next stage of development.
29.4 Maternal gene products establish
gradients in early embryogenesis
Figure 29.5 Translation
of a localized mRNA
generates a gradient of
protein as the products
diffuses away from the
site of synthesis.
29.5 Anterior
development uses
localized gene regulators
Figure 29.6 Mutant embryos that
cannot develop can be rescued by
injecting cytoplasm taken from a
wild-type embryo,The donor can
be tested for time of appearance and
location of the rescuing activity; the
recipient can be tested for time at
which it is susceptible to rescue and
the effects of injecting material at
different locations.
29.5 Anterior
development uses
localized gene regulators
Figure 29.7 Bicoid protein
forms a gradient during D,
melanogaster development
that extends for ~200 mm
along the egg of 500 mm.
29.5 Anterior
development uses
localized gene regulators
Figure 29.7 Bicoid protein
forms a gradient during D,
melanogaster development
that extends for ~200 mm
along the egg of 500 mm.
29.5 Anterior
development uses
localized gene regulators
Figure 29.17 In each axis-determining system,localized
products in the egg cause other maternal RNAs or proteins
to be broadly localized at syncytial blastoderm,and zygotic
RNAs are transcribed in bands at cellular blastoderm.
29.5 Anterior development uses
localized gene regulators
Figure 29.8 The
posterior pathway
has two branches,
responsible for
abdominal
development and
germ cell formation.
29.6 Posterior development uses
another localized regulator
Figure 29.2 The early
development of the
Drosophila egg occurs in a
common cytoplasm until the
stage of cellular blastoderm.
29.6 Posterior
development uses
another localized
regulator
Figure 29.6 Mutant embryos that
cannot develop can be rescued by
injecting cytoplasm taken from a
wild-type embryo,The donor can
be tested for time of appearance
and location of the rescuing
activity; the recipient can be
tested for time at which it is
susceptible to rescue and the
effects of injecting material at
different locations.
29.6 Posterior
development uses another
localized regulator
Figure 29.9 nanos products are
localized at the posterior end of a
Drosophila embryo,The upper
photograph shows the tightly
localized RNA inthe very early
embryo (at the time of the 3rd
nuclear division),The lower
photograph shows the spreadingof
nanos protein at the 8th nuclear
division,Photographs kindly
provided by Ruth Lehmann.
29.6 Posterior
development uses another
localized regulator
Figure 29.10 Some mRNAs are
transported into the Drosophila
egg as ribonucleoprotein
particles,They move to their
final sites of localization by
association with tracks that may
be either either microtubules or
actin filaments.
29.7 How are mRNAs and
proteins transported and
localized?
Figure 29.11 Dorsal and ventral
identities are first distinguished
when grk mRNA is localized
on the dorsal side of the oocyte,
Synthesis of Grk activates the
receptor coded by torpedo,
which triggers a MAPK
pathway in the follicle cells.
29.8 Dorsal-ventral
development uses
localized receptor-
ligand interactions
Figure 29.4 Each of the four maternal systems that functions in the egg is initiated
outside the egg,The pathway is carried into the egg,where each pathway has a
localized product that is the morphogen,This may be a receptor or a regulator of
gene expression,The final component is a transcription factor,which acts on
zygotic targets that are responsible for the next stage of development.
29.8 Dorsal-ventral development uses
localized receptor-ligand interactions
Figure 29.12 Wild-type Drosophila
embryos have distinct dorsal and
ventral structures,Mutations in
genes of the dorsal group prevent the
appearance of ventral structures,and
the ventral side of the embryo is
dorsalized,Ventral structures can be
restored by injecting cytoplasm
containing the Toll gene product.
29.8 Dorsal-ventral
development uses
localized receptor-
ligand interactions
Figure 29.13 The dorsal-ventral
pathway is summarized on the right
and shown in detail on the left,It
involves interactions between
follicle cells and the oocyte,The
pathway moves into the oocyte
when spatzle binds to Toll and
activates the morphogen,The
pathway is completed by
transporting the transcription factor
dorsal into the nucleus.
29.8 Dorsal-ventral
development uses
localized receptor-
ligand interactions
Figure 29.14 Activation of IL1
receptor triggers formation of a
complex containing adaptor(s) and
a kinase,The IRAK kinase
activates NIK,which
phosphorylates I-kB,This triggers
degradation of I-kB,releasing NF-
kB,which translocates to the
nucleus to activate transcription.
29.8 Dorsal-ventral
development uses
localized receptor-
ligand interactions
Figure 21.2 The activity of a
regulatory transcription factor
may be controlled by synthesis
of protein,covalent
modification of protein,ligand
binding,or binding of
inhibitors that sequester the
protein or affect its ability to
bind to DNA.
29.8 Dorsal-ventral
development uses
localized receptor-
ligand interactions
Figure 29.15 Dorsal protein forms a
gradient of nuclear localization from
ventral to dorsal side of the embryo,On the
ventral side (lower) the protein identifies
bright nuclei; on the dorsal side (upper) the
nuclei lack proteDorsal protein forms a
gradient of nuclear localization from
ventral to dorsal side of the embryo,On the
ventral side (lower) the protein identifies
bright nuclei; on the dorsal side (upper) the
nuclei lack protein and show as dark holes
in the bright cytoplasm,
29.8 Dorsal-ventral
development uses
localized receptor-
ligand interactions
Figure 29.16
Dorsal-ventral
patterning
requires the
successive
actions of
three localized
systems.
29.8 Dorsal-ventral development uses
localized receptor-ligand interactions
Figure 29.17 In each axis-determining system,localized
products in the egg cause other maternal RNAs or proteins
to be broadly localized at syncytial blastoderm,and zygotic
RNAs are transcribed in bands at cellular blastoderm.
29.8 Dorsal-ventral development uses
localized receptor-ligand interactions
Figure 26.35 Activation
of TGFb receptors
causes phosphorylation
of a Smad,which is
imported into the
nucleus to activate
transcription.
29.9 TGF/BMPs are diffusible morphogens
Figure 29.18
The morphogen
dpp forms a
gradient
originating on
the dorsal side
of the fly
embryo,This
prevents the
formation of
neural
structures and
induces
mesenchymal
structures.
29.9 TGF/BMPs are diffusible morphogens
Figure 29.19 Two
common pathways
are used in early
development of
Xenopus,The
Niewkoop center
uses the Wnt
pathway to induce
the Spemann
organizer,The
organizer diffuses
dorsalizing factors
that counteract the
effects of the
ventralizing BMPs.
29.9 TGF/BMPs are diffusible morphogens
Figure 29.20 The TGFb/Bmp
signaling pathway is conserved in
evolution,The ligand may be
sequestered by an antagonist,which
is cleaved by a protease,Ligand
binds to a dimeric receptor,causing
the phosphorylation of a specific
Smad,which together with a Co-
Smad translocates to the nucleus,to
activate gene expression.
29.9 TGF/BMPs are
diffusible morphogens
Gap in DNA is the absence
of one or more nucleotides
in one strand of the duplex.
29.10 Cell fate is determined by compartments
that form by the blastoderm stage
Figure 29.21 Drosophila
development proceeds through
formation of compartments
that define parasegments and
segments.
29.10 Cell fate is
determined by
compartments that form by
the blastoderm stage
Figure 29.22
Segmentation genes affect
the number of segments
and fall into three groups.
29.10 Cell fate is
determined by
compartments that form
by the blastoderm stage
Figure 29.23
Maternal and
segmentation genes
act progressively on
smaller regions of
the embryo.
29.10 Cell fate is
determined by
compartments that form
by the blastoderm stage
Figure 29.24 Expression of the
gap genes defines adjacent
regions of the embryo,The gap
genes control the pair-rule
genes,each of which is
expressed in 7 stripes.
29.10 Cell fate is
determined by
compartments that form
by the blastoderm stage
Figure 29.25 ftz
mutants have half the
number of segments
present in wild-type,
Photographs kindly
provided by Walter
Gehring.
29.10 Cell fate is determined by compartments
that form by the blastoderm stage
Figure 29.26 Transcripts of the ftz gene are localized in stripes
corresponding to even numbered parasegments,The expressed regions
correspond to the regions that are missing in the ftz mutant of the
previous figure,Photograph kindly provided by Walter Gehring.
29.10 Cell fate is determined by compartments
that form by the blastoderm stage
Figure 29.27 The eve stripe in
parasegment 3 is activated by
hunchback and bicoid,Repression
by giant sets the anterior boundary;
repression by Kruppel sets the
posterior boundary,Mulltiple
binding sites for these proteins in a
480 bp region of the promoter
control expression of the gene.
29.10 Cell fate is
determined by
compartments that form
by the blastoderm stage
Figure 29.28 Simultaneous staining
for ftz (brown) and eve (grey)
shows that they are first expressed
as broad alternating stripes at the
time of blastoderm (upper),but
narrow during the next 1 hour of
development (lower),Photographs
kindly provided by Peter Lawrence.
29.10 Cell fate is
determined by
compartments that form
by the blastoderm stage
Figure 29.29 Engrailed protein is localized in nuclei and
forms stripes as precisely delineated as 1 cell in width,
Photograph kindly provided by Patrick O'Farrell.
29.10 Cell fate is determined by compartments
that form by the blastoderm stage
Figure 29.30 Reciprocal interactions maintain Wg and Hg signaling between adjacent
cells,Wg activates a receptor,which activates a pathway leading to translocation of
Arm to the nucleus,This leads to expression of Hedgehog protein,which is secreted
to act on the neighboring cell,where it maintains Wg expression.
29.11 The wingless/wnt signaling pathway
Figure 29.31 Wg secretion is assisted by
porc,Wg activates the Dfz2 receptor,
which inhibits Zw3 kinase,Active Zw3
causes turnover of Arm,Inhibition of
Zw3 stabilizes Arm,allowing it to
translocate to the nucleus,In the nucleus,
Arm partners Pan,and activates target
genes (including engrailed),A similar
pathway is found in vertebrate cells
(components named in blue).
29.11 The wingless/wnt
signaling pathway
Figure 29.19 Two common pathways are used in early development of Xenopus,The
Niewkoop center uses the Wnt pathway to induce the Spemann organizer,The organizer
diffuses dorsalizing factors that counteract the effects of the ventralizing BMPs.
29.11 The wingless/wnt signaling pathway
Homeotic genes are defined by
mutations that convert one body
part into another; for example,an
insect leg may replace an antenna.
29.12 Complex loci are extremely
large and involved in regulation
Figure 29.32 The homeotic
genes of the ANT-C complex
confer identity on the most
anterior segments of the fly,
The genes vary in size,and
are interspersed with other
genes,The antp gene is very
large and has alternative
forms of expression.
29.12 Complex loci are
extremely large and
involved in regulation
Figure 29.33 A four-winged fly is produced by a triple mutation in abx,bx,
and pbx at the BX-C complex,Photograph kindly provided by Ed Lewis.
29.12 Complex loci are extremely
large and involved in regulation
Figure 29.34 The bithorax (BX-
C) locus has 3 coding units,A
series of regulatory mutations
affects successive segments of
the fly,The sites of the
regulatory mutations show the
regions within which deletions,
insertions,and translocations
confer a given phenotype.
29.12 Complex loci are
extremely large and
involved in regulation
Figure 29.34 The bithorax (BX-
C) locus has 3 coding units,A
series of regulatory mutations
affects successive segments of
the fly,The sites of the
regulatory mutations show the
regions within which deletions,
insertions,and translocations
confer a given phenotype.
29.12 Complex loci are
extremely large and
involved in regulation
Figure 29.34 The bithorax (BX-
C) locus has 3 coding units,A
series of regulatory mutations
affects successive segments of
the fly,The sites of the
regulatory mutations show the
regions within which deletions,
insertions,and translocations
confer a given phenotype.
29.12 Complex loci are
extremely large and
involved in regulation
Homeobox describes the conserved sequence
that is part of the coding region of D,
melanogaster homeotic genes; it is also found
in amphibian and mammalian genes expressed
in early embryonic development.
Paralogs are highly similar proteins that are
coded by the same genome.
29.13 The homeobox is a common
coding motif in homeotic genes
Figure 21.3 Transcription factor SP1 has a series of three
zinc fingers,each with a characteristic pattern of cysteine
and histidine residues that constitute the zinc-binding site.
29.13 The homeobox is a common coding
motif in homeotic genes
Figure 21.11 The homeodomain of the Antennapedia gene represents the major
group of genes containing homeoboxes in Drosophila; engrailed (en) represents
another type of homeotic gene; and the mammalian factor Oct-2 represents a
distantly related group of transcription factors,The homeodomain is
conventionally numbered from 1 to 60,It starts with the N-terminal arm,and
the three helical regions occupy residues 10-22,28-38,and 42-58.
29.13 The homeobox is a common coding
motif in homeotic genes
Figure 21.9 TR and RAR bind the
SMRT corepressor in the absence
of ligand,The promoter is not
expressed,When SMRT is
displaced by binding of ligand,
the receptor binds a coactivator
complex,This leads to activation
of transcription by the basal
apparatus.
29.13 The homeobox is
a common coding motif
in homeotic genes
Figure 21.10 The
homeodomain may be the
sole DNA-binding motif in
a transcriptional regulator
or may be combined with
other motifs,It represents a
discrete (60 residue) part of
the protein.
29.13 The homeobox is a common coding
motif in homeotic genes
Figure 29.35 Mouse and human
genomes each contain 4 clusters of
genes that have homeoboxes,The
order of genes reflects the regions in
which they are expressed on the
anterior-posterior axis,The Hox genes
are aligned with the fly genes
according to homology,which is
strong for groups 1,2,4,and 9,The
genes are named according to the
group and the cluster,e.g.,HoxA1 is
the most anterior gene in the HoxA
group,All Hox genes are present in
both man and mice except for some
mouse genes missing from cluster C
(indicated by half boxes).
29.13 The homeobox is a common coding
motif in homeotic genes
Figure 29.36 A comparison of ANT-
C/BX-C and HoxB expression patterns
shows that the individual gene products
share a progressive localization of
expression towards the more posterior
of the animal proceeding along the
gene cluster from left to right,
Expression patterns show the regions
of transcription in the fly epidermis at
10 hours,and in the central nervous
system of the mouse embryo at 12 days.
29.13 The homeobox is a
common coding motif in
homeotic genes
Figure 29.36 A comparison of ANT-
C/BX-C and HoxB expression patterns
shows that the individual gene products
share a progressive localization of
expression towards the more posterior
of the animal proceeding along the
gene cluster from left to right,
Expression patterns show the regions
of transcription in the fly epidermis at
10 hours,and in the central nervous
system of the mouse embryo at 12 days.
29.13 The homeobox is a
common coding motif in
homeotic genes
1,The development of segments in Drosophila occurs by
the actions of segmentation genes that delineate
successively smaller regions of the embryo,
2,Each of the 4 maternal systems consists of a cascade
which generates a locally distributed or locally active
morphogen.
3,The major anterior-posterior axis is determined by two
systems,the anterior system establishes a gradient of bicoid
from the anterior pole; and the posterior system produces
nanos protein in the posterior half of the egg.
4,The early embryo consists of a syncytium,in which
nuclei are exposed to common cytoplasm.
29.14 Summary
5,Three gap genes are zinc-finger proteins,and one is a
basic zipper protein,
6,Homeotic genes impose the program that determines
the unique differentiation of each segment,
7,The genes of the ANT-C and BX-C loci,and many
segmentation genes (including the maternal gene bicoid
and most of the pair-rule genes) contain a conserved
motif,the homeobox,
8,Drosophila genes containing homeoboxes form an
intricate regulatory network,in which one gene may
activate or repress another.
29.14 Summary
