* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Chapter 21. Development of Multicellular Organisms Sydney
Gene desert wikipedia , lookup
Gene therapy wikipedia , lookup
Essential gene wikipedia , lookup
Epigenetics of diabetes Type 2 wikipedia , lookup
Epigenetics in learning and memory wikipedia , lookup
Long non-coding RNA wikipedia , lookup
X-inactivation wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
History of genetic engineering wikipedia , lookup
Oncogenomics wikipedia , lookup
Gene therapy of the human retina wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Point mutation wikipedia , lookup
Genome evolution wikipedia , lookup
Gene expression programming wikipedia , lookup
Ridge (biology) wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Mir-92 microRNA precursor family wikipedia , lookup
Biology and consumer behaviour wikipedia , lookup
Genomic imprinting wikipedia , lookup
Minimal genome wikipedia , lookup
Microevolution wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Genome (book) wikipedia , lookup
Designer baby wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Chapter 21. Development of Multicellular Organisms Sydney Brenner, 1960 Mutation vs. variation Mutation Variation Mutation Types of mutation 1. No phenotype -Amorph 2. Loss of function -Null -Hypomorph 3. Gain of function -Hypermorph -Antimorph (dominant negative) 1. Robust model for the behavior of individual and identified cells 1000 somatic + 1000-2000 germ cells 2. Convenient model for genetics Single heterozygote worm can produce homozygous progeny 3. Cell fates and lineages are almost perfectly predictable Mechanisms for C. elegans development • Polarity formation by maternal effectors • Cell-cell interactions to make complex patterns • Heterochronic genes • Apoptosis 1. Maternal effect genes • mRNA from mother is asymmetrically distributed along anteroposterior axis Par (partitioning defective) genes bring P granules to posterior pole One cell having P granule give rise to germ cells 2. Cell-cell interactions to make complex patterns 2. Cell-cell interactions to make complex patterns • P2-EMS interaction: 1. Mom mutants without gut -Mom gene (Wnt) expressed in P2 cell -Frizzled gene (Wnt receptor) expressed in EMS cells 2. Pop mutants with extraguts -Pop genes encode LEF-1/TCF homolog -Reduced pop activity gut -Increased Pop activity muscle Cells change over time in their responsiveness to signals • At four cells Anterior cell specification depend on Notch signals • At 12-cell stage, both Aba and Abp progenitors exposed to Notch signals Granddaughter of Aba cells induce pharynx Granddaughter of Abp cells unresponsive to Notch Heterochronic genes control the timing of development • Heterochronic phenotypes: The cells in a larva of one stage behave as though they belong to a larva of a different stages, or cells in the adult carry on dividing as though they belonged to a larva • lin-4 for the transition larval stage1 3 • let-7 for the transition late larva adult Apoptosis • 1030-131 • Cell death abnormal gene -ced-3, ced-4, egl-1 (caspase, Apaf-1, BAD homolog) cause cell death -ced-9 (Bcl-2 homolog) repress cell death The Nobel Prize in Physiology or Medicine 2002 "for their discoveries concerning 'genetic regulation of organ development and programmed cell death'" Sydney Brenner 1/3 of the prize H. Robert Horvitz 1/3 of the prize John E. Sulston 1/3 of the prize United Kingdom USA United Kingdom The Molecular Sciences Institute Berkeley, CA, USA Massachusetts Institute of Technology (MIT) Cambridge, MA, USA The Wellcome Trust Sanger Institute Cambridge, United Kingdom b. 1927 (in Union of South Africa) b. 1947 b. 1942 Drosophila and the molecular genetics of pattern formation: Genesis of the body plan Seymor Benzer Overall procedures Overall procedures Syncytial Specification Pole cells Maternal effects • Egg polarity determination • A-P and D-V axis Cytoplasmic bridges Egg polarity genes (Maternal effectors) Egg polarity genes (Maternal effectors) Dorsoventral axis Dorsal protein (NF-kB): -Dorsally, the protein is present in the cytoplasm and absent from the nuclei; ventrally, it is depleted in the cytoplasm and concentrated in the nuclei. -Toll gene controls the redistribution Dorsoventral specification Dorsal protein concentration High activate twist, repress dpp (decapentaplegic) Intermediate sog (short gastrulation) Dorsolventral specification Fate map • Distribution of twist in mesodermal cells Anteroposterior specification • Maternal genes, bicoid, nanos • Segment genes refine the pattern – – – – Zygotic genes Six gap genes: Coarse subdivision Pair rule genes: Segment alteration Segment-polarity genes: Homeotic selector genes Anteroposterior specification • Krupel lacks 8 segments (T1-A5) • Even-skipped (eve) lacks oddnumbered parasegments • Fushi tarazu (ftz) lacks even-numbered parasegments • Gooseberry posterior half is the mirror image of anterior half Pair rule genes • Formation of parasegments • Expression pattern of ftz (brown) and eve (gray) Segment polarity genes • Forms parasegments polarity • Involves cell-cell interactions • Associated with two signaling pathways – Wnt – Hedgehog Regulatory hierarchy The Nobel Prize in Physiology or Medicine 1995 "for their discoveries concerning the genetic control of early embryonic development" Edward B. Lewis 1/3 of the prize Christiane Nüsslein-Volhard Eric F. Wieschaus 1/3 of the prize 1/3 of the prize USA Federal Republic of Germany USA California Institute of Technology Pasadena, CA, USA Max-Planck-Institut für Entwicklungsbiologi e Tübingen, Federal Republic of Germany Princeton University Princeton, NJ, USA b. 1918 d. 2004 b. 1942 b. 1947 Homeotic mutations Homeotic selector genes • Hox gene complex – Antennapedia complex – Bithorax complex • Contain homeodomain – 60 amino acids – DNA binding region • Regulate positional information Hox gene complex Expression of hox gene complex Hox gene complex Comparison of hox gene expression Comparison of hox gene expression Organogenesis and patterning of appendage • Methods in fly genetics: Somatic mutations Mosaic • Methods in fly genetics: Enhancer trap Imaginal discs • Groups of cells set aside undifferentiated • 19 discs (9 pairs + 1 genital) • Develop into organs such as leg, wing, eyes etc. Specific ID genes define organs • Distal-less expressed in appendages • Pax-6 expression in eyes Wing formation • Sector formation in wing disc • Four compartments foms • engrailed, apterous genes are involved Wing formation Wing formation (A) The shapes of marked clones in the Drosophila wing reveal the existence of a compartment boundary. The border of each marked clone is straight where it abuts the boundary. Even when a marked clone has been genetically altered so that it grows more rapidly than the rest of the wing and is therefore very large, it respects the boundary in the same way (drawing on right). Note that the compartment boundary does not coincide with the central wing vein. (B) The pattern of expression of the engrailed gene in the wing, revealed by the same technique as for the adult fly shown in Figure 21–40. The compartment boundary coincides with the boundary of engrailed gene expression. Limb formation Bristle formation • achaete, scute genes -HLH -Proneural genes Scute expression in wing disc Lateral inhibition • Notch-delta Lateral inhibition Notch somatic mutation Loss of lateral inhibition Bristle patches Bristle formation • Numb gene -Block Notch gene activity Bristle formation • Planar polarity genes • Orienting bristle backward position • frizzled proteins control planar polarity • dishevelled downstream of frizzled Bristle formation