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Drosophila and Syncitial Specification Early Cleavage Stages • Syncytial blastoderm – Superficial cleavage – 13 cycles of rapid nuclear divisions (8 min) – Each nucleus surrounded by microtubules and microfilaments – Future germ cells cellularize first (pole cells) • Cellular blastoderm – 6000 cells – 4 hrs. post fertilization Nuclear Migration Segmentation of Embryo and Adult What Specifies A-P Segmentation? • How does this pattern arise? • How are anterior-posterior and dorsal-ventral axes established? • How is a segmented pattern generated along the anterior-posterior axis? • How is each segment differentiated from the others? What is the Evidence for Early Polarity • Anterior half and posterior half of embryo have different potentials shortly after fertilization – ligation experiments • Cut in half gives ends but no middles – “organizing centers” at anterior and posterior ends? – interference with anterior organizing center • UV or RNase • embryos lack head and thorax • develop mirror symmetric abdomen and ends • Suggests “morphogens” that exist in concentration gradients • What are the morphogens? How Do You Find the Morphogens Genetically? • Christiane Nusslein-Volhard began a genetic approach (1980s) • Identify (screen for) mutations that cause defects in embryonic polarity and classify – Maternal-effect • bicoid, hunchback (embryo with no head and thorax region) • nanos, caudal (embryo with no posterior abdominal region) • torso, torso-like (embryo with no ends) – Zygotic-effect • Regulated by above A Maternal Anterior Determinant: Bicoid • bicoid mutant phenotype: • bicoid mRNA is placed into the oocyte asymmetrically • mRNA attaches to microtubules in anterior Oogenesis Polarity • Adult ovariole: Mechanism of Bcd mRNA Localization How Does Bicoid Get To Anterior? • Oocyte gerkin protein tells terminal follicle cells to be posterior • Posterior follicle cells signal to activate protein kinase A in oocyte membrane • Controls MT orientation (+ end toward posterior) • Bicoid mRNA 3’ UTR binds to exuperantia and swallow that bind to dynein – go to anterior • (Other mRNAs bind to kinesin) – to go to posterior) Where is Bicoid Protein Found? Protein gradient is more extensive than mRNA Translation occurs after fertilization Comparison of Gradients What Happens if mRNA Is Misplaced? • Evidence that BCD is sufficient to initiate anterior development: What Happens If Gradient Shape Is Altered? • Evidence that BCD concentration is important for placement of segments • swallow and exuperantia mutants: – BCD gradient is not as sharp • Or overexpress bcd ant post wt A H T Ab Te exu H T Ab Te A Maternal Posterior Determinant: Nanos • nanos phenotype is opposite of bicoid: – Required for posterior development • mRNA is asymmetrically localized – At posterior end – Kinesin bound oskar mRNA and staufen protein – Staufen allows translation of oskar which binds nanos mRNA at posterior – Nanos protein gradient What Do Morphogens Do? • bicoid and nanos regulate gene expression of other maternal RNAs: – hunchback – caudal What Do Morphogens Do? • Bicoid inhibits translation of caudal mRNA • Nanos inhibits translation of hunchback Setting Up AP Gradients What Do Morphogens Do? • 2 ant -> post gradients • 2 post -> ant gradients of proteins • bicoid, caudal, hunchback act as transcriptional regulators of zygotic genes A Third Set of Maternal mRNAs: Terminal Genes • Terminal group: torso and torso-like – mutants lack extreme anterior and posterior structures (acron and telson) What Type of Protein is Torso? • Made in ovarian cells and mRNA placed into oocyte – torso RNA and protein are evenly distributed – torso = RTK, a transmembrane protein • Constitutive mutant (always on) converts whole anterior to acron and posterior to telson – So must be spatially activated What Activates Torso? • Torso-like • Not expressed in oocyte, but in follicle cells • Only in anterior and posterior • Protein secreted and activates torso locally What Does Torso Signal? • Torso RTK causes phosphorylations that ultimately inactivate groucho protein • Groucho is transcriptional inactivator of some zygotic genes needed for specification of ends • Inhibiting an inhibitor activates