Animal Development Regulation of gene expression

Transcription

1 Animal Development Regulation of gene expression Prof. Ilan Davis, Department of Biochemistry. Wellcome Trust Research Senior Fellow Senior Research Fellow, Jesus College

2 References Molecular Biology of the Cell Alberts et al. Sixth Edition Chapter 6: How cells read the genome Chapter 7: Control of Gene Expression Chapter 21: Development of Multicellular Organisms Chapter 22: Stem Cells and Tissue Renewal Subcellular mrna localisation at a glance Richard M. Parton, Alexander Davidson, Ilan Davis, Timothy T. Weil (2014) J Cell Sci 127: ; doi: /jcs

3 Content of lectures 1 1. Multicellular development 2. Single cell egg to Organism 3. Cells - same DNA, different gene expression 4. Transcriptional factors 5. The central dogma - modified 6. The RNA World hypothesis 7. Post-transcriptional regulation gene expression 8. Splice isoforms - neurons 9. Translational regulation 10. Mechanism and function of mrna localisation

4 Multicellular animal development evolved on planet earth

5 Central question in developmental biology: Axis specification How does a complex animal develop from a single cell - the fertilised egg?

6 How does a whole organism develop from a single cell? Axis specification in frogs Molec. Biol of the Cell

7 Different cells contain the same DNA Each cell type expresses a different set of genes

8 Different cells contain different proteins

9 Regulation of gene expression by transcription factors

10 Central dogma

11 An RNA enzyme The three-dimensional structure of the original ribozyme, the self-splicing intron of Tetrahymena (13). Green and blue ribbons indicate the path of the RNA backbone in the two major domains of the RNA, and the red star marks the active site. Figure by Feng Guo

12 How did life arise on our planet? The RNA world hypothesis

13 Multiple levels of regulation of gene expression Post-transcriptional regulation (at level of RNA) is still under appreciated in development

14 Splice Isoforms

15 Splice Isoforms

16 Dendritic Arbarisation Neurons in Drosophila larvae Chun Han lab (Cornell)

17 Translational regulation Translational regulation in time and space is crucial for many developmental processes

18 Translational regulation in development Repressors and activators Poly A length -long poly A is translated mirnas Processing bodies (P bodies)

19 Processing bodies

20 Intracellular mrna localisation

21 + Repression of translation unlocalised mrna mrna degredation Export mrna sorting Localisation By MT motors - Anchoring by actin?

22 Functions of asymmetric cytoplasmic mrna localisation 1) Target proteins to their site of function. 3) Define the axes of the embryo. 2) Segregate cytoplasmic determinants during asymmetric cell division 4) Promote or Restrict protein diffusion in a syncytial embryo (morphogenetic gradients)

23 The Importance of RNA localisation Essential for many fundamental processes: Cell polarity Developmental patterning Neural development Learning and memory Hamilton et al 2012, Biophysics for the life sciences Chapter 11

24 mrna localization in Xenopus oocytes and mesoderm induction An1-4 mrna Vg-1, Vg-T mrna (and many others) animal Dug Melton Yoel Israeli Kim Mowry vegetal

25 mrna localization targets actin to its site of function at the leading edge actin mrna and protein Robert H Singer Zip code 3 UTR Oligonucleotides - disrupt localization and motility Zip code binding protein (ZBP)

26 mrna localisation controls mating type switching in budding yeast Kim Nasmyth Robert H Singer Ira Herskovich Ralf Jansen Ash1 mrna and yeast mating type switch She mutants She 1: Myo4 is a TYPE V MYOSIN She 2: dsrna-binding protein binds to the localization signals She 3: adaptor that bridges the myosin heavy chain and She2 M D

27 Specifying stem cell identity and state in asymmetrically dividing neural stem cells Chris Doe Andrea Brand Juergen Knoblich Prospero - a conserved transcription factor that regulates stem cell renewal and differentiation in Drosophila neural stem cells and in a number of different vertebrate stem cell models.

28 cis-acting RNA signals and transacting proteins link the mrna to molecular motor for transport MTs kinesin actin myosin MTs Linkers? Staufen She2+3 BicD Egalitarian dynein/ dynactin mrna

29 Thanks Any questions?

30 Copyright Notice Staff and students of this university are reminded that copyright subsists in a number of diagrams in this presentation, and the work from which it was taken. This Digital Copy has been made under the terms of a CLA licence which allows you to: - access and download a copy; - print out a copy. The Digital Copy and any digital or printed copy supplied to or made by you under the terms of this Licence are for use in connection with this Course of Study. You may retain such copies after the end of the course, but strictly for your own use. All copies (including electronic ones) shall include this Copyright Notice and shall be destroyed and/or deleted if and when required by the University. Except as provided for by copyright law, no further copying, storage or distribution (including by ) is permitted without the consent of the copyright holder. The author (which term includes artists and other visual creators) has moral rights in the work and neither staff nor students may cause, or permit, the distortion, mutilation or other modification of the work, or any other derogatory treatment of it, which would be prejudicial to the honour or reputation of the author. Course of Study: Molecular and Cellular Biochemistry, Year 3 Name of Designated Person authorising scanning: Prof. Ilan Davis All textbooks and individual references to primary or review papers in this lecture 30