Model of Drosophila Anterior-Posterior Pattern Formation
Maternal effect genes
Zygotic genesSyncytial blastoderm
Cellular blastoderm
Homeotic selector genesSimilar signal into different structures—
Different interpretation—controlled by Hox genes
Homeotic transformation of the wing and haltere
Homeotic genes—mutated into homeosis transformationAs positional identity specifiers:Bithorax-haltere into wing
Imaginal discs and adult thoracic appendages
Bithorax mutation—Ubx misexpressed T3 into T2 –anterior haltere into Anterior wing
Postbithorax muation (pbx)—Regulatory region of the Ubx—Posterior of the haltere into wing
The spatial pattern of expression of genes of the bithorax complex
Bithorax—Ultrabithorax –5-12 Abdominal-A—7-13 Abdominal-B—10-13
Bithorax mutant –PS 4 default state+Ubx—5,6+Abd-A—7,8,9+Abd-B—10Combinatorial mannerLack Ubx—5,6 to 4 also 7-14 thorax structure in the abdomen
Hox—gap, pair-rule for the first 4 hours, then polycomb (repression), and Trithorax (activation)
Regulatory elements
Segmental identity of imaginal disc
Antennapedia—expressed in legs, but not in antennaIf in head, antennae into legs
Hth (homothorax) and Dll (distal-less)—expressed in antennae and legIn antenna: as selector to specify antennaIn leg: antennapedia prevents Hth and Dll acting together
Dominant antennapedia mutant (gene on)—blocks Hth and Dll in antennae disc, so leg formsNo Hth, antenna into leg
Fly and mouse/human genomes of homeotic genes
Expression pattern and the location on chromosome
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.
Egg chamber formation
Specifying the Anterior-Posterior Axis of the
Drosophila Embryo During Oogenesis
Specifying the Anterior-Posterior Axis of the
Drosophila Embryo During Oogenesis
Protein kinase A orients the microtubules
Before fertilization ligand immobilized
Small quantities—bound to torso at the poles little left to diffuse
Anterior/posterior extremities
Terminal structure-acron., telson, most posterior abdominal segment
Torso---receptor tyrosine kinaseLigand---trunk
Torso signaling
Groucho: repressorHuckenbein, tailless are released from transcriptional suppression
The EGFR signal establishes the A/P and D/V axial pattern
Gurken—TGFTorpedo--- EGFR
The EGFR signal establishes the A/P and D/V axial pattern
Red-actinGreen-gurken proteinAs well as mRNA
The expression of EGFR pathway target gene
The localization of Gurken RNA
Cornichon, and brainiac-Modification and Transportation of the protein
K10, squid localize gurken mRNA
Cappuccino and spire –cytoskeleton ofthe oocyte
The Key determinant in D/V polarity is pipe mRNA in follicle cells
Cross section
windbeutel—ER protein pipe—heparansulfate 2-o-sulfotransferase (Golgi) nudel—serine protease
The activation of Toll
Perivitelline space
Fig. 31-16
The dorsal-ventral pathway
Maternal genes—Fertilization to cellular blastodermDorsal system—for ventral structure(mesoderm, neurogenic ectoderm)
Toll gene product rescue the defectToll 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
Toll pathway
Without Toll activationDorsal + cactusToll activation –tube (adaptor) and pelle (kinase)Phosphorylate cactus and promote its degradation
B cell gene expressionDorsal=NF-kBCactus=I-kB
The mechanism of localization of dorsal protein to the nucleus
Dorsalization mutation
The activation of NF-B by TNF-
Fig. 31-17
The dorsal-ventral pathways
Dorsal nuclear gradientActivates—twist, snail (ventral)Represses—dpp, zen (dorsal)
Fig. 31-19
Toll protein activation results in a gradient of intranuclear dorsal protein
Spatzle is processed in the periviteline space after fertilization
Zygotic genes pattern the early embryoDorsal protein activates twist and snail represses dpp, zen, tolloid
Rhomboid----neuroectodermRepressed by snail (not most ventral)
Binding sites for dorsal protein in their regulatory regions
Model for the subdivision of the dorso-ventral axis into different regions by the gradient in nuclear dorsal protein
Dorsalized embryo—Dorsal protein is not in nucleiDpp is everywhereTwist and snail are not expressed
Threshold effect—integrating Function of regulatory binding sites
Regulatory element=developmental switches
High affinity (more dorsal region-low conc.)
Low affinity (ventral side-high conc.)
Nuclear gradient in dorsal protein
Dpp protein gradient
Cellularization---signal through transmembrane proteinsDpp=BMP-4(TGF-)Dpp protein levels high, increase dorsal cellsShort of gastrulation (sog) prevent the dpp spreading into neuroectodermSog is degraded by tolloid (most dorsal)
Smad= Sma + MadSma-C. elegansMad-Fly
1. Antagonist2. Proteases
Fig. 31-24
The TGK-/Bmp signaling pathway
dpp: decapentaplegic
Fig. 31-23
The Wnt and BMP pathways are used in early development
Signal Pathways Induced by Cellular Surface Receptors
Mol. Cell. Biol. 5th ed. 2004, Lodish et al.
Type I, II receptor-Ser/Thr phosphorylation
The Smad-dependent pathway activated by TGF-
Colorectal cancer: type II receptorPancreatic cancers: 50% Smad
One component between receptor and gene regulation
The Smad-dependent pathway activated by TGF-
De-repression of target genes in Dpp signaling
Nature reviews genetics-8-663-2007
Structural and Functional Domains of Smad Family
TGFb , Activin: R-Smad 2,3BMPs: R-Smad 1, 5, 8Common Smad4-nucleocytoplasmic shuttling, DNA bindingInhibitory Smads: I-Smad 6, 7
Cell, 95,737,1998
13,216, 2003
NLS , NES
Smad4 shuttles between the cytosol and nucleus
Inhibitory Smads: I-Smad 6, 7
—recruting Smurf (ubiquitin ligase to receptor)
Cell, 95,737,1998
2005, 17:107
Different internalization pathwaysresulted in distinct cellular effects
Models of morphogen gradient formation
Fig. 31-11, 12, 13sharpen
Integration of two signal pathways at the promoter
Cell,95,737, 1998SBE: Smad binding elementARE: activin-response elementTRE: TPA-response element (AP-1 binding)XBE: transcription X
Smad2 and FAST Smad3 and c-Jun/cFos
Fig. 31-21
The axis determining systems
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