Model of Drosophila Anterior-Posterior Pattern Formation

1
Model of Drosophila Anterior-Posterior Pattern
Formation
Maternal effect genes
Zygotic genes Syncytial blastoderm
Cellular blastoderm
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Homeotic selector genes Similar signal into
different structures Different
interpretationcontrolled by Hox genes
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Homeotic transformation of the wing and haltere
Homeotic genesmutated into homeosis
transformation As positional identity
specifiers Bithorax-haltere into wing
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Imaginal discs and adult thoracic appendages
Bithorax mutationUbx misexpressed T3 into T2
anterior haltere into Anterior wing
Postbithorax muation (pbx) Regulatory region of
the Ubx Posterior of the haltere into wing
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The spatial pattern of expression of genes of
the bithorax complex
BithoraxUltrabithorax 5-12
Abdominal-A7-13
Abdominal-B10-13 Bithorax mutant PS 4 default
state Ubx5,6 Abd-A7,8,9 Abd-B10 Combinatoria
l manner Lack Ubx5,6 to 4 also 7-14 thorax
structure in the abdomen Hoxgap, pair-rule for
the first 4 hours, then polycomb (repression),
and Trithorax (activation)
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Regulatory elements
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Segmental identity of imaginal disc
Antennapediaexpressed in legs, but not in
antenna If in head, antennae into legs
Hth (homothorax) and Dll (distal-less)expressed
in antennae and leg In antenna as selector to
specify antenna In leg antennapedia prevents Hth
and Dll acting together Dominant antennapedia
mutant (gene on) blocks Hth and Dll in antennae
disc, so leg forms No Hth, antenna into leg
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Fly and mouse/human genomes of homeotic genes
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Expression pattern and the location on chromosome
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Egg chamber formation
A/P during oogenesis the oocyte move towards one
end in contact with follicle cells. Both the
oocyte and the posterior follicle cells express
high levels of the E-cadherin If E-cadherin is
removed, the oocyte is randomly positioned. Then
the oocyte induces surrounding follicle cell to
adopt posterior fate.
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Specifying the Anterior-Posterior Axis of the
Drosophila Embryo During Oogenesis
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Specifying the Anterior-Posterior Axis of the
Drosophila Embryo During Oogenesis
Protein kinase A orients the microtubules
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Anterior/posterior extremities
Torso---receptor tyrosine kinase Ligand---trunk
Terminal structure- acron., telson, most
posterior abdominal segment
Before fertilization ligand immobilized Small
quantitiesbound to torso at the poles
little left to diffuse
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Torso signaling
Groucho repressor Huckenbein, tailless are
released from transcriptional suppression
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The EGFR signal establishes the A/P and D/V
axial pattern
GurkenTGFa Torpedo--- EGFR
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The EGFR signal establishes the A/P and D/V
axial pattern
Red-actin Green-gurken protein As well as mRNA
The expression of EGFR pathway target gene
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The localization of Gurken RNA Cornichon, and
brainiac- Modification and Transportation of the
protein K10, squid localize gurken
mRNA Cappuccino and spire cytoskeleton of the
oocyte
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The Key determinant in D/V polarity is
pipe mRNA in follicle cells
Cross section
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The activation of Toll
windbeutelER protein   pipeheparansulfate
2-o-sulfotransferase (Golgi)   nudelserine
protease
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The dorsal-ventral pathway
Perivitelline space
Fig. 31-16
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Toll pathway
Maternal genes Fertilization to cellular
blastoderm Dorsal systemfor ventral
structure (mesoderm, neurogenic ectoderm) Toll
gene product rescue the defect Toll mutant
dorsalized (no ventral structure) 2.
Transfer wt cytoplasm into Toll mutant
specify a new dorsal-ventral axis (injection
site ventral side) spatzle (ligand) fragment
diffuses throughout the space
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The mechanism of localization of dorsal protein
to the nucleus
Without Toll activation Dorsal cactus Toll
activation tube (adaptor) and pelle
(kinase) Phosphorylate cactus and promote its
degradation B cell gene expression DorsalNF-kB C
actusI-kB
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Dorsalization mutation
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The activation of NF-kB by TNF-a
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The dorsal-ventral pathways
Fig. 31-17
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Dorsal nuclear gradient Activatestwist, snail
(ventral) Repressesdpp, zen (dorsal)
Fig. 31-19
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Toll protein activation results in a gradient of
intranuclear dorsal protein
Spatzle is processed in the periviteline space
after fertilization
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Model for the subdivision of the dorso-ventral
axis into different regions by the gradient in
nuclear dorsal protein
Zygotic genes pattern the early embryo Dorsal
protein activates twist and snail
represses dpp, zen, tolloid Rhomboid----n
euroectoderm Repressed by snail (not most ventral)
Binding sites for dorsal protein in their
regulatory regions
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Nuclear gradient in dorsal protein
Dorsalized embryo Dorsal protein is not in
nuclei Dpp is everywhere Twist and snail are not
expressed Threshold effectintegrating Function
of regulatory binding sites Regulatory
element developmental switches High affinity
(more dorsal region-low conc.) Low affinity
(ventral side-high conc.)
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Dpp protein gradient
Cellularization---signal through transmembrane
proteins DppBMP-4(TGF-b) Dpp protein levels
high, increase dorsal cells Short of gastrulation
(sog) prevent the dpp spreading into
neuroectoderm Sog is degraded by tolloid (most
dorsal)
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The TGK-b/Bmp signaling pathway

1. Antagonist
2. Proteases

dpp decapentaplegic
Smad Sma Mad Sma-C. elegans Mad-Fly
Fig. 31-24
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The Wnt and BMP pathways are used in early
development

• Fig. 31-23

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Signal Pathways Induced by Cellular Surface
Receptors
Mol. Cell. Biol. 5th ed. 2004, Lodish et al.
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The Smad-dependent pathway activated by TGF-b
Type I, II receptor-Ser/Thr phosphorylation
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The Smad-dependent pathway activated by TGF-b
Colorectal cancer type II receptor Pancreatic
cancers 50 Smad One component between receptor
and gene regulation
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De-repression of target genes in Dpp signaling
Nature reviews genetics-8-663-2007
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Structural and Functional Domains of Smad Family
TGFb , Activin R-Smad 2,3 BMPs R-Smad 1, 5,
8 Common Smad4-nucleocytoplasmic shuttling, DNA
binding Inhibitory Smads I-Smad 6, 7
Cell, 95,737,1998
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Smad4 shuttles between the cytosol and nucleus
NLS , NES
13,216, 2003
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Inhibitory Smads I-Smad 6, 7 recruting Smurf
(ubiquitin ligase to receptor)
Cell, 95,737,1998
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Different internalization pathways resulted in
distinct cellular effects
2005, 17107
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Models of morphogen gradient formation
sharpen
Fig. 31-11, 12, 13
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Integration of two signal pathways at the
promoter
Smad2 and FAST
Smad3 and c-Jun/cFos
Cell,95,737, 1998
SBE Smad binding element ARE activin-response
element TRE TPA-response element (AP-1
binding) XBE transcription X
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The axis determining systems
Fig. 31-21