Slide 1Slide 2Slide 3Slide 4Slide 5Slide 6Slide 7Anterior-Posterior Pattern Formation in FliesSlide 9Slide 10Remember that cleavage starts without cell division in Drosophila (superficial cleavage)Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25The Homeotic genes in DrosophilaAntennapedia expression is negatively regulated by the Bithorax complex homeotic proteinsSlide 28Bithorax complex homeotic proteinsSlide 30Slide 31Slide 32Slide 33Slide 34Slide 35Slide 36Slide 37Slide 38Slide 39Slide 40Slide 41Slide 42Flies are quick!The fly body plan: each segment has a unique identity and produces distinctive structures3 head3 thorax8 abdomenModel Organisms: Drosophila• small (adult < 5 mm long). Can keep hundreds in a small vial.• short generation time - 8 days• embryo develops outside the body in a short time - so can easily study development• history - scientists have been doing genetics and collecting mutations for many years (since 1910)• very cheap to keep• reproducible anatomy• segmentation visible• many anatomical, developmental, & behavioral similarities to vertebratesSmall Genome = 120 MbThomas Hunt Morganand the white eye mutant wildtype flywhite mutantChristiane Nüsslein-Volhard and Eric Wieschaus used genetics to identify proteins that set up the embryonic body planWieschaus and Nüsslein-Volhardlooked for mutants that affect the fly body plan wildtypeThe fruit fly body plan is self-assembled in 24 hours: how is it specified?Anterior-Posterior Pattern Formation in FliesFigure 9.17Maternal effect genesMaternal effect genes establish theanterior/posterior axis of the embryoPosterior Determinantnanos mRNAAnterior Determinantbicoid mRNAOocytenurse cellsbicoid protein accumulates in a gradient 1000Level of bicoidA Phead tailRemember that cleavage starts without cell division in Drosophila (superficial cleavage)Fig. 9.1Syncytial specification: specification by interactions between cytoplasmic regions rather than cellsGene A- turned on only by high level of bicoid Gene B- turned on only by intermediate level of bicoid Gene C- turned off by bicoid and thus only on where bicoid is absentA gradient of the bicoid transcription factor turns on different genes at different "thresholds" bicoidwildtype larvabicoid mutantbicoid mutants have no head!!Figure 9.23The “bicoid target genes” are known as the gap genesHunchbackKrüppelKnirpsExpression pattern of proteins encoded by gap genesGap gene mutants are missing different regions of the bodyHunchbackKrüppelThe gap genes depend on each other to form boundaries and provide identity to unique regions where they overlapFig. 9.17The transcription factors encoded by gap genes cooperate to create even more complex patterns of gene expressionExpression domain of HunchbackThe expression domains of Hunchback and Krüppel overlap Some genes require both Hunchback and Krüppel present to be turned on Expression domain of KrüppelAlberts Chapter 8 (p. 266)Pair-rule genes, such as Even-skipped, refine the segmentsThe segment-polarity gene Engrailed is activated by the Even-skipped and Fushi tarazu pair-rule transcription factorsFigure 9.33Anterior-Posterior Pattern Formation in FliesFigure 9.17Maternal effect geneswildtypeAntennapedia mutantEd Lewis was far ahead of his time …Ultrabithorax mutantFigure 9.36WildtypeFig. 9.28Is Ubx is expressed at the right time and place to make T3 different from T2? Yes! Ubx is expressed in T3 and A1Experiment #1Ultrabithorax is expressed in the region of the embryo that will become the 3rd thoracic and 1st abdominal segmentsIn these segments, the Ultrabithorax protein acts as a transcription factor, turning on genes specific for the 3rd thoracic and 1st abdominal segments T3 specific geneA1 specific geneT1 specific geneA5 specific geneOFFOFFONONExperiment #2Does Ultrabithorax bind DNA and regulate genes specific for T3 and A1?The Homeotic genes in DrosophilaFig 9.35ANT-C BX-CAntennapedia expression is negatively regulated by the Bithorax complex homeotic proteinsFig 9.35ANT-C BX-CWildtypeUbx abdA AbdB triple mutantT2T3A1A8T2T2T2T2All abdominal segments take on a T2 identity if the bithorax complex is deletedBithorax complex homeotic proteinsFig 9.35ANT-C BX-CUltrabithorax, abdA, and AbdBnormally repress expression of the thorax-specific “leg gene” Distalless in the abdominal segmentswild-type Ubx abdA AbdB triple mutantT1 T2 T3abdomenLewis hypothesizedthat the duplicationand diversificationof homeotic master regulatorsunderlies the evolution ofan increasingly complexbody planThe human body is alsobuilt up fromreiterated units (segments)with different identities alongthe A/P axisMammals also have homeotic genesexpressed at different places along the A/P axisMouse homeotic genes also encode homeodomain transcription factors that act as master regulators of segment identity Hox 3.1 is expressed in the region of the embryo that will become the 12th and 13th ribs In these segments, Hox 3.1 protein acts as a transcription factor that turns on genes specific for the 12th and 13th ribs12th rib specific gene13th rib specific gene4th rib specific gene15th rib specific geneOFFOFFONONNotch and the competition to be a neuronThe story of the epidermal vs. neural cell fate decision in Drosophila They started as one big happy ectodermal epithelium… I feel the need to be a neuroblast! you guys stay here and keep up the good work! then one of their number got some big ideas and started to ingress inside…as it left, it sent a message to its neighbors, telling them to stick with the epidermal fateWhen the story takes a turn for the worse … the fly neurogenic mutants (mastermind, big brain, notch, delta)Nervous systemEpidermisExtra nervous systemNo epidermis! Some cells become neuroblasts and signal their neighbors to remain epidermis If signal is missing...all cells eventually ingress and become neuroblastsNotch and Delta encode related transmembrane proteins but Delta lacks a large intracellular domainDelta Lipid bilayerInside OutsideNotch+++mutant+++++++mutantmutant++++++++++++++Cells lacking signal behave differently than cells lacking receptor If mutant cells lack signal, they can be rescued by wild type neighbors which make signal.If mutant cells lack receptor, they cannot be rescued by wild type neighbors which make signal.+++mutant+++++++mutantmutant++++++++++++++Thanks, I needed that!What? I can't hear
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