A Fly by Any Other Name …
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Transcript of A Fly by Any Other Name …
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A Fly by Any Other Name …
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Developmental Genetics
• Drosophila is one of the best understood developmental model systems
• Genome sequenced – 1999
• 100s of characterized mutant strains
• Easily maintained & propagated
• Large, easily manipulated embryos
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GastrulationVentral Views Dorsal View
Ventral Furrow
Cephalic Fold
Pole Cells
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Germ Band Extension & RetractionFull Extension RetractedLateral Views
Note Segmentation
Mandibular
Maxillary
Labial
T1
T2
T3
A1
A1
A8
A7
A6
A5
A4A3
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1st Instar LarvaCuticle
Denticle Bands
Telson
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Morphogenesis
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Segmentation in Larva & Adult
Thorax
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Hierarchy of Gene Expression
Maternal Effect Genes
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Localization of Proteins
Maternal Effect Genes - Bicoid Gap Genes Hunchback (orange), Krüppel (green)
Pair-rule Genes - Fushi tarazu Segment Polarity Genes - Engrailed
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Maternal Effect Genes
• Maternally transcribed genes• mRNA transported and localized within oocyte• Anterior Group
– Bicoid (bcd), Hunchback (hb)
• Posterior Group– Nanos (nos), caudal (cad)
• Termini Group– Torso (tor), torso-like (tlk)
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Identification of Three Polarity Gradients in Drosophila
• 1980• Christiane Nüsslein-Volhard• Eric Wieschaus• Initiated mutagenic screen for developmental
regulatory genes• One of 1st genes identified caused an anterior defect• Went on to identify mutations causing posterior &
termini defects as well as dorsal-ventral polarity defects
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Bicoid Anterior Mutations
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Bicoid Anterior Mutations
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Three A-P Morphogens
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Protein Gradients from Maternal Effect Genes
•Bcd mRNA localized to anterior, nos mRNA localized to posterior, cad & hb mRNAs unlocalized
•Bcd blocks translation of cad in ant compartment•Nos blocks translation of hbin posterior compartment•Localized translation of bcd & nos causes secondary gradients of hb & cad proteins
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Pathways of A-P Patterning
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Initial Establishment of A-P Axis by Gurken Signaling
• Posterior pole is 1st region to be specified– Polarized organization of microtubules
– Localization of maternal mRNAs and proteins
• Oocyte nucleus 1st positioned at posterior pole– Gurken (grk) protein translated in perinuclear regions
– grk protein accumulates in posterior and activates the RTK torpedo in follicle cells
• Gurken is an EGF homolog• Torpedo is an EGF Receptor homolog
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Posterior specification by grk/tor signaling
Activated tor in posterior follicle cells
alters cell adhesion between follicle cells
and oocyte in turn repolarizing
microtubules in oocyte which move nucleus to the future
dorsal side
On dorsal side, grk/tor signal sets off dorsal specification pathway
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Localization of Maternal Posterior Determinants
• Grk induced repolarization of microtubules results in scaffolding for oskar localization
• Localization of oskar directs localization of tudor, vasa, and valois
• These proteins in turn bind and localize nanos mRNA
• Nos mRNA remains untranslated until fertilization due to masking by the protein smaug
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Function of Posterior Morphogen Nanos
• Translational Repressor– Represses translation of bcd & hb– Requires pumilio (pum) as co-factor– Pum binds bcd and hb 3’ UTRs – Alone pum promotes pA addition – Pum recruits nos to 3’ UTR which then promotes
deadenylation of bcd and hb preventing translation
• Nos & osk are also required for formation of pole plasm (germ plasm)
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Localization of Maternal Anterior Determinants
• Bicoid is localized by exuperantia (exu), exuperantia-like (exl), and swallow (swa) proteins– Exl binds bcd mRNA– Exu binds exl & bcd mRNA – Swa binds the bcd-exl-exu mRNP– Swa binds microtubules thus anchoring the
entire complex of mRNA and proteins
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Function of Anterior Morphogen Bicoid
• Transcriptional Activator & Repressor– Activates transcription of hunchback and some
gap genes– Represses transcription of some gap genes,
pair-rule genes, and segment polarity genes
• Translational Repressor– Repressed translation of caudal mRNA
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Specification of the Terminal Segments
• Acron – anterior most segment
• Telson – posterior most segment
• Both regions are specified with via the same signaling pathway
• Torso – RTK expressed ubiquitously in oocyte
• Torso-like – ligand expressed only in posterior and anterior follicle cells
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Specification of Termini
groucho represses transcription of tailless and huckbein.
Tor signal pathway inhibits groucho allowing tll & hkb to function
These proteins specify both termini.
bcd + hkb + tll defines acronw/o bcd, tll & hkb specify telson