Presentation on theme: "The Parts and the Whole: How Genes Allow an Animal to Build Itself Itai Yanai Biology, Technion."— Presentation transcript:
The Parts and the Whole: How Genes Allow an Animal to Build Itself Itai Yanai Biology, Technion
"The ship wherein Theseus and the youth of Athens returned had thirty oars, and was preserved by the Athenians down even to the time of Demetrius Phalereus, for they took away the old planks as they decayed, putting in new and stronger timber in their place, insomuch that this ship became a standing example among the philosophers, for the logical question of things that grow; one side holding that the ship remained the same, and the other contending that it was not the same." —Plutarch, Theseus The parts relative to the whole: The ship of Theseus
The Development of an Animal http://www.wormclassroom.org/files/worm/EmbryoHatch.swf
Introducing C. elegans C. elegans is studied as a model organism for a variety of reasons. It is a a multicellular eukaryotic organism that is simple enough to be studied in great detail. Strains are cheap to breed and can be frozen. When subsequently thawed they remain viable, allowing long-term storage.
Research from the humble worm has proved fruitful 3 Nobel Prizes in the past 10 years
The development of the nematode C. elegans is comprised of five somatic founder lineages
C MS E P3 ABs Expresses the genes expected from the gut Evidence for mosaic development: segregation of developmental potential in the embryo Dissociate cells Laufer, Bazzicalupo and Wood. Cell 1980
C MS E P3 ABs Expresses the genes expected from the gut Evidence for mosaic development: segregation of developmental potential in the embryo Dissociate cells med-1,2 end-1,3 elt-2,7 Maduro & Rothman. Dev. Bio. 2002
ABa ABp Makes half of the pharynx ABp ABa Evidence for regulative development: blastomere swapping experiment Priess and Thomson. Cell 1987
Rachelly Normand Bioinformatician Dr. Tal Katz-Ezov Head of Center Dr. Maayan Duvshani-Eshet Head of LS&E Infrastructure Unit Yvgenia Lapis Lab technician Maya Abraham Bioinformatician Karen Chait Bioinformatician Anastasia Diviatis Lab technician Noa Henig Bioinformatician With generous support from:
Now possible to gauge gene expression levels for all genes by sequencing the transcriptome. Reads genome sequence lowly expressed gene highly expressed gene
Which genes are expressed at which time in development? Levin, Hashimshony, Wagner and Yanai. Developmental Cell (2012)
Time Which genes are expressed at which time in development? Gene expression levels Different genes
Stage 7 in mid-development that is uniquely conserved across different nematodes.
Hashimshony, Wagner, Sher and Yanai. Cell Reports (2012) Our lab developed a method for single cell RNA-Seq
.... Gene 1 Gene 2 Gene 3 Gene 20,000 Cell 1 Cell 2 Cell 3 Our lab developed a method for single cell RNA-Seq high low Expression n level
Using the method we can identify differential expression between the sister cells mex-3 Bowerman et al. Cell 1996
Hashimshony, Wagner, Sher and Yanai. Cell Reports (2012) CEL-Seq for multiplexed single cell RNA-Seq CEL-Seq is a single cell transcriptomics method using in vitro transcription. CEL-Seq is linear, sensitive and reproducible. CEL-Seq is highly multiplexed allowing for the parallel examination of hundreds of cells.
The evolution of pathways can be studied by comparing across distantly related species
Currently we are studying an entire phylum with Tardigrades as an outgroup.
Vlad GrishkevichShay Ben-ElazarAvital PolskyDavid SilverMartin Feder Our group at the Technion Gal AvitalNaftalie Senderovich Natalia Mostov Leon Anavy Michal Levin Sally Khair Dr. Tamar Hashimshony Assist. Prof. Itai Yanai
AB P 1 The vitellogenins are expressed in the whole embryo but not in the cells, even early on. Whole Parts No expressionHigh expression
GLP-1/Notch P0P0 P1P1 P2P2 EMS ABp ABa AB APX-1/Delta How is the pharynx programmed? A first Notch signal is received by ABp but not ABa glp-1 apx-1
GLP-1/Notch P0P0 P1P1 P2P2 EMS ABp ABa AB APX-1/Delta hlh-27 tbx-37,38 lag-2 How is the pharynx programmed? Without the signal, no hlh-27 and extra lag-2 and tbx-37,38 hlh-27 lag-2 tbx-37,38
GLP-1/Notch P0P0 P1P1 P2P2 EMS ABp ABa AB APX-1/Delta MSE ABa descendants GLP-1/Notch DSL-1??/Delta tbx-37,38lag-1 pha-4 ceh-22 Anterior Posterior lag-1 is present throughout though, another signal is missing? lag-1 ceh-22 pha-4
GLP-1/Notch P0P0 P1P1 P2P2 EMS ABp ABa AB APX-1/Delta MSE ABa descendants GLP-1/Notch DSL-1??/Delta tbx-37,38lag-1 pha-4 ceh-22 Anterior Posterior tbx-35 pha-4 med-1,2 MS descendants Why doesn’t the MS blastomere make pharynx? pha-4 tbx-35
How many genes overall are missing? Fraction covered (log2) Number of genes
Sulston et al. Dev. Bio. 1983 C. elegans development proceeds by an invariant cell lineage
C. elegans embryos develop according to an invariant cell lineage P0
500 bp Chromosome II CEL-Seq reads have “sense” orientation
The expression of many genes is lineage specific Whole embryo Developmental stages Exp. level