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Gradients, cascades, and signaling pathways

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1 Gradients, cascades, and signaling pathways
Chapter 31 Gradients, cascades, and signaling pathways Development of the Drosophila body plan Genetic studies One of the best understood developmental systems 13,600 genes Axis determination Signaling pathway Transcriptional and translational regulation Principles of Development 2nd edition, by Lewis Wolpert (Chapter 5) The genetics of axis specification in Drosophila The Chapter 9 of Developmental Biology by Scott Gilbert, 7th edition Chang-Gung University Dr. Li-Mei Pai

2 Targeted ectopic expression of the Eyeless gene --induce eyes to develop in locations such as legs and antennae Closely related genes initiate the development program for the same organ in animals separate by 500 million years of evolution

3 Life cycle of Drosophila 4 stages: embryo, larva, pupa, adult
Culture condition: 250C and 60% humidity

4 Body patterning of fly One cell to an organism Fig. 31-1

5 Homogeneous egg to asymmetry
---control of gene expression (spatial and temporal) Asymmetric division Asymmetric distribution of cytoplasmic component Maternal genes Segmentation genes Homeotic genes

6 Early development of Drosophila

7 Transgenic flies

8 Model of Drosophila Anterior-Posterior Pattern Formation
Maternal effect genes Zygotic genes Syncytial blastoderm Figures\Chapter09\DevBio7e09081.jpg Cellular blastoderm

9 Maternal effect genes—( do not damage mother)
preformed mRNA and proteins in the egg Zygotic genes—embryo nuclei


11 Polarization of the body axes during oogenesis
each egg chamber: 3 types of cells Oocyte with nucleus (germinal vesicle-GV) Connected to 15 nurse cells }---germ-line Surrounded by a monolayer of about 1000 somatic follicle cells

12 Female sterile mutation
Somatic cells Germline cells Genetic analyses Biochemical assays

13 Fig. 31-4

14 The effects of mutations in the maternal gene system
Three classes Anterior Posterior terminal head and thoracic abdominal acron and telson

15 Three independent Genetic Pathways Interact to Form the Anterior-Posterior Axis of the Drosophila Embryo Figures\Chapter09\DevBio7e09101.jpg

16 Three independent Genetic Pathways Interact to Form the Anterior-Posterior Axis of the Drosophila Embryo Figures\Chapter09\DevBio7e09102.jpg


18 Morphogen----cell structure

19 Bicoid gene is necessary for the establishment of the anterior structure
Bicoid--Transcribed in nurse cells, transported into the oocyte, localized at the anterior( 3’UTR) fertilized—translated Protein diffuses and forms morphogen gradient No head and thoracic If prick at the anterior of normal egg Partial rescued Bicoid mutant + wt anterior cytoplasm— wt head

20 Gene copy number

21 Repression of nanos mRNA
translation outside of posterior Hb-repressor of transcription (of Abdominal gene) Hb is required for thorax structure, and is absent in posterior Nanos---prevent Hb translation— mRNA degraded—knirps and Giant expression

22 Posterior determination
Nanos ( and pumilio) suppresses the translation Of the maternal mRNA of Hunchback Zygotic hb establishes a Gradient If maternal hb is absent, nanos is no more needed


24 Fate map Information—maternal regulators Refined—zygotic genes Region—compartment 14 parasegments (gastrulation)— Eg. 8=A2P+A3A


26 Every other segment

27 The target genes of hunchback
Increase dose of hunchback – kruppel shift posteriorly Gap: 1) respond to the Bicoid 2) regulate one another


29 Phenotype of pair rule mutant

30 Expression of pair rule gene

31 Regulation of pair rule genes

32 Pair rule genes The mRNA is uniformly expressed,
but protein synthesis is blocked— specific degradation of mRNA Stripes develop, transcription ceases Ftz promoter respond to other pair-rule genes Fig

33 Segment polarity-engrailed

34 Engrailed- transcription factor homeodomain

35 Intercellular signaling set up PS boundary

36 Segment polarity A/P axis within one segment
Ventral epidermis of the abdomen—ventral denticle belts (anterior) Mutation—alter the denticle pattern Wingless=Wnt hedgehog Principles of Development by Lewis Wolpert Oxford university press Second edition, 2002

37 Signals controlling cuticle pattern
Principles of Development by Lewis Wolpert

38 Fig

39 Cell, 127, 469, 2006

40 Colon cancer-APC Oncogenic-c-myc Cell, 127, 469, 2006

41 Wg distributed asymmetrically—
less in posterior (endocytosis and degradation) Until early stage 10, Wingless spreads into the engrailed domain and then recedes sometime during stage 10. At stage 12, Wingless-containing vesicles are infrequently detected in engrailed-expressing cells. At this stage, rhomboid begins to be expressed at the posterior of each engrailed stripe, leading to the activation of EGFR signaling in and around its domain of expression. The zone of Rhomboid influence corresponds roughly to where denticles form at the end of embryogenesis, while Wingless signaling is associated with the absence of denticles (bald cuticle). PS, parasegment boundary; SB, segment boundary.

42 Different pathways that transduce Wnt signals
Camadulin Planar polarity-hair pointed direction Cell, 109, 271, 2002

43 Intercellular signaling set up PS boundary
Developmental Biology by Scott F. Gilbert Sinauer Associates, publishers Six edition, 2000

44 The domains of expression of the segment polarity genes
Patched is not in en cells Principles of Development by Lewis Wolpert



47 The hedgehog signaling pathway
Without signal—Ci is processed as a repressor into nucleus With signal---full length Ci acts as an activator in the nucleus Principles of Development by Lewis Wolpert

48 Reading reference : Wnt/b-Catenin signaling in Development and disease Cell, 127, , 2006

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