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Axis Specification I

Axis Specification I. The Maternal-Effect Mutants. (also found the D/V Group). Nusslein-Volhard, 2004. bicoid mRNA oskar mRNA protein + nanos RNA. microtubule-based - + . A-P polarity set up in egg chamber. maternal.

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Axis Specification I

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  1. Axis Specification I

  2. The Maternal-Effect Mutants (also found the D/V Group) Nusslein-Volhard, 2004

  3. bicoid mRNA oskar mRNA protein + nanos RNA microtubule-based - + A-P polarity set up in egg chamber

  4. maternal The Maternal A/P Information BCD is a transcription factor and a translation factor (represses Caudal translation) NANOS is a translation factor (represses Hunchback translation) The Terminal System BCD NANOS

  5. The Zygotic Genes Nusslein-Volhard and Wieschaus, Nature 1980 Wieschaus Nobel Lecture, 1995

  6. Creating Complex Patterns From Simple Ones maternal zygotic BCD Gradient GAP Genes HB = Red, KR = Green Pair Rule Gene (fushi tarazu) Segment Polarity (engrailed)

  7. Complex Patterns From Simple Ones: Gap Genes BCD Giant Kruppel

  8. Creating Complex Patterns From Simple Ones 3 Maternal “Systems” for A/P maternal zygotic ≈11 Gap Gene Domains 8 Pair-rule genes x 7 stripes = 56 domains ftz eve

  9. Generating Precise Positional Information Along Axes Dave Kosman

  10. Understanding Transcriptional Control of Patterning: The Story of eve Levine and colleagues eve is a pair rule gene--expressed in 7 “stripes” How is this pattern created? Step 1: “Promoter bashing” to identify relevant enhancers ftz eve eve Stripe 2 enhancer--lacZ S. Small eve Stripe 3/7 enhancer--lacZ

  11. Studying Transcriptional Control of Development Step 3: Use biochemistry to identify direct regulators Eve Step 1: “Promoter bashing” to identify relevant enhancers Step 2: Use expression patterns and genetics to identify candidate regulators eve stripe 2 Gt Step 4: In vivo proof: mutating cis binding sites should cause same change in expression as mutating trans regulators Kr Small, Blair and Levine EMBO 1992

  12. Eisen Lab PMID: 18584029 Sepsidae (scavenger flies) ≈100 mya

  13. Eisen Lab PMID: 18584029

  14. Eisen Lab PMID: 18584029

  15. Positional Information in the Embryo Controls: Segment Identity (Making Segments Different From One Another) Segmentation and Pattern Within a Segment

  16. Wg Hh Segment Polarity Genes -wg and hh Signaling Pathways -Establish 14 Segmental Boundaries -Act as morphogens to pattern within each segment

  17. Positional Information in the Embryo Controls: Segment Identity (Making Segments Different From One Another) Segmentation and Pattern Within a Segment

  18. Fun with Flies! Homoeosis (Bateson 1894): alteration of one organ of a segmental or homologous series from its own characteristic form to that of another member of the series “homoeotic mutants” Ultrabithorax Antenae to Leg Leg to Antenae Proboscis to Leg Haltere to Wing Wing to Haltere Genitalia to Leg Ed Lewis

  19. Homeotic (Hox) genes are expressed differentially along the A/P Axis Specify segment identity

  20. Drosophila Mouse

  21. Drosophila Hypothetical common ancestor Amphioxus Mouse

  22. Regulation of Segment Identity by a “Hox Code” Wild Type T2 T3 Antp ON Antp OFF Ubx OFF Ubx ON Wing Haltere Ubx mutant T2 T3 Antp ON Antp ON Ubx OFF Ubx OFF Wing Wing Ultrabithorax Wing Haltere UBX Expression

  23. Mammals Are Segmented Too Cervical Thoracic Lumbar Sacral

  24. 5/6 mutant Triple homozygote A/a C/c D/c X A/a C/c D/c 1/64 pups = aaccdd Hox Genes Specify A/P Identity in Vertebrates Wellik and Capecchi, 2003

  25. Patterning the Dorsal-Ventral Axis Maternal-Effect Mutants: The D/V Group D wt P A V Dorsalized Ventralized

  26. A. Courey D/V Patterning Establishes the Mesodermal Identity Determined by twist and snail Toll pathway: on on ventral side

  27. It is not birth, marriage or death, but gastrulation, which is truly the most important time in your life.               - Lewis Wolpert (1986) Gastrulation

  28. Drosophila gastrulation The mesoderm and endoderm invaginate separately (a bit unusual) Ventral View

  29. ? Cell Biology Cell Division/Death Cell Adhesion Cell Movement Cell Shape Cell Adhesion and Cell Sorting Cell Identity Morphogenesis

  30. The Cell Biology of Fly Mesoderm Gastrulation Epithelial-mesenchymal transition (EMT) Apical constriction Invagination Migration/spreading

  31. folded gastrulation and concertina Effect Apical Constriction twist and snail folded gastrulation (ligand) Apical constriction fog expression in mesoderm is dependent on twist and snail GPCR? Concertina(G alpha) RhoGEF

  32. Rho Kinase myosin Myosin relocalizes from basal to apical at the time of apical constriction Apical constriction folded gastrulation and concertina Affect Gastrulation twist and snail folded gastrulation (ligand) T48 GPCR? Concertina(G alpha) fog RhoGEF

  33. DE-cadherin May Regulate EMT in the Drosophila Mesoderm Epithelial-mesenchymal transition (EMT) snail DE-cadherin EMT

  34. FGF Signaling Promotes Mesoderm Migration (FGFR)

  35. How Cell Identity Controls Morphogenesis of Gastrulation Cell Identity (twist, snail) fog, T48 FGF-R Cell Adhesion E-Cadherin? Migration Epithelial-mesenchymal transition (EMT) Apical constriction

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