1 DEVELOPMENTAL SYSTEMS I FALL 2015 SCHEDULE Course numbers: NYUMC: NYU: BMSC-GA 2610 BIOL-GA 2130 Time: Tuesdays: 2-5 PM lecture, Fridays: 2:00-4:30PM discussion In addition students meet in small groups (self-organized) to discuss the papers between the lecture and discussion section Locations: NYUMC: NYU: Skirball Institute, 4th floor conference room Room 1009G Silver Center, Conference room in the Biology Dept. office Depending on the week, the course will either be held in the Skirball building at NYUMC or in the NYU Biology Department at Washington Square. The NYU Shuttle bus, Route E, travels between NYUMC and NYU. Route F also stops a few blocks from NYUMC. DS I COURSE DESCRIPTION This course is an introduction into Developmental Genetics. Fundamental questions, concepts and methodologies of modern inquiry into the genetic and cellular mechanisms of development will be explored through lectures and discussion of primary literature. Topics include embryonic axis determination and the establishment of cellular asymmetry, cell specification through cellcell interaction and region-specific gene expression, morphogenesis and organogenesis in different species. The first week will cover key molecular and genetic techniques used to study Developmental Biology in a variety of model organisms. From the second week on, two instructors will discuss current topics in developmental biology. Each session includes a lecture and discussion part. In the discussion part students will discuss research articles related to the topic. Lecture outlines and discussion assignments will be posted on the course website (on ALEX) at least one week before class. Students will read ~2 research articles as well as review article(s) or book chapter(s) for each session. Each student is required to read the articles before each session and to be able to present a summary, a detailed description of the data, underlying techniques and figures, and a critique of the research papers. You will be called upon to explain experimental methods, results and interpretation of results in the papers. To facilitate discussion, students will meet in small groups Wednesday or Thursday to discuss the papers. These meetings are self-organized by the students. The recommended text/reference book is: Developmental Biology by Scott Gilbert. You are strongly encouraged to take advantage of the textbook as well as assigned review articles before the lecture class to acquaint yourself with each topic prior to the lecture. The 6th edition (2000) of the Gilbert text is available on the web via the NCBI website “books” link: http://www.ncbi.nlm.nih.gov/books/NBK9983/ While some material is not covered in the Gilbert text, where possible, we have listed relevant chapters from the web-accessible 6th edition of Gilbert. More recent editions (8th ed., 2006; 9th 2 2010; 10th ed., 2013) are available with additional content and are listed below as recommended. The 8th edition is available at low cost online. In addition each student will write a five page (not including references) research proposal. Proposals should be sent by email as “.doc” or “.pdf” files to jeremy.nance@med.nyu.edu by **5pm on December 11th** The proposal should relate to a topic discussed in the sessions and should be organized into: An Introduction which provides background information, introduces the current knowledge in the field and states the questions and goals addressed by the proposed experiments. An Experimental procedure/result section describes an experiment with an interpretable outcome (no fishing expeditions, please!). The experiment should be experimentally feasible, material for the experiment should either be easy to produce or already available. The experimental procedures used should be described clearly and potential problems should be addressed. In the Discussion section, the possible outcomes of the experiment and their interpretations should be discussed. The topic of the proposal should not be directly related to the student’s project or past work in any capacity either previous research, during rotation, as a technician, or in his/her lab. That is, the topic should use a model organism the student hasn’t worked with, if possible, and definitely not the one they are using for their thesis research. If someone has a particular problem (for example, they have worked with every model organism), please contact me. The paper must be written independently in your own words. Both active participation throughout the course and the research proposal contribute to the final grade. Date 9/4/15 Lecturer(s) Jeremy Nance/ Nick Stavropoulos Topic Introduction to concepts, organisms and techniques in Developmental Genetics – compared and contrasted in model organisms (more details on mouse in week 4) Model organisms Part 1: Flies Genetic nomenclature Genetic screens Transgenesis Mosaic animals and cell autonomy Location NYUMC 9/8/15 Matt Rockman/ Holger Knaut Model organisms Part 2: Worms and Fish Genetic nomenclature Genetic screens Transgenesis Mosaic animals and cell autonomy NYUMC 9/11/15 NO CLASS (NYU Biol. Retreat) 9/15/15 Jeremy Nance/ Patrick Eichenberger Polarity: (B. subtilis and C. elegans) Binary fission, asymmetric cell division Coordination of cell cycle and cytokinesis Generating A-P polarity; PAR proteins, NYU 3 No Gilbert for bacteria Gilbert Ch. 8 (pp. 251-257) 9/18/15 09/22/15 Eichenberger/ Nance Steve Small/ Jeremy Dasen Gilbert ch. 9 09/25/15 09/29/15 Small/Dasen Adrian Erlebacher Including paper discussion Gilbert ch. 11 and Parts of ch 4, 5 and 19 Gilbert ch 7 10/02/15 Ruth Lehmann Including paper discussion Rho signaling, actin, myosin and cytoskeletal control Techniques/experimental concepts: maternal effect phenotypes, RNAi, reporter fusions and antibody staining Discussion NYU Segmentation in Drosophila and Vertebrates Pre-planning the Drosophila body in the embryo. Area-specific transcription in the early embryo. Refinement of pattern via a transcriptional cascade. Target gene responses to gradients. Complex promoters. Independent activity of multiple enhancers that use a common basal promoter. SYSTEMS ASPECTS Classical experiments: Segmentation screens and the proposal of a patterning cascade. bcd activation of hb (DNA-binding, cotransfection, reporter genes). eve promoter dissection, and stripe 2 regulation. NYU Discussion From egg to embryo in mice; ES cells and reprogramming fertilization blastocyst, implantation, decidualization, reproductive endocrinology Axis specification Tools static, video – markers, Lineage tracing (physical versus genetic marking), Cell ablation Chimeras, Knockout mice, Forward and reverse genetics ES cells and Stem cell lines from early embryos, cloning From egg to embryo in flies Polarity and Morphogen gradients Maternal effects Preformation/prepattern Localized determinants RNA localization by microtubules and Translational control NYU NYUMC NYUMC 4 10/06/15 Jessica Treisman/ Cindy Loomis Gilbert ch. 15-16 Gilbert ch. 18 10/9/15 10/13/15 10/16/15 10/20/15 Treisman /Loomis Claude Desplan/ Anna Di Gregorio Gilbert 8th edition: ch. 10 (pp.359-367) ch 20 (pp. 890-715) Desplan/ Di Gregorio Jeremy Nance/ Lionel Christiaen Gilbert ch. 8-10 Appendage development; compartments and developmental fields Imaginal disc development compartments boundaries organizers Limb development: Early specification of limb field Subsequent autonomous outgrowth and patterning proximal-distal outgrowth and AER anterior-posterior patterning and ZPA dorsal-ventral patterning and non-AER ectoderm Differentiation of musculoskeletal and skin structures Discussion Evolution and Development Conservation of eye development Regressive (eye) evolution Evolution of vision NYUMC Discussion NYU Gastrulation, morphogenesis and organogenesis (worm, fly, Xenopus, zebrafish, Ciona, mouse) Gastrulation in C. elegans, Drosophila, fish, amphibians and mouse Convergent extension, apical constriction Morphogenesis and organogensis Signaling pathways and adhesion that regulate gastrulation, morphogenesis, and organogenesis Morphogenesis (migration, proliferation, looping) Cardiac specification, heart fields Multipotent cardiovascular progenitors, differentiation, heart stem cells Conserved cardiac gene network (“kernel”) Heart evolution in chordates NYUMC Concepts/techniques: Explants Maternal-effect vs. embryonic phenotypes Organizer NYUMC NYU 5 10/23/15 10/27/15 Nance/ Christiaen Jessica Treisman/ Erika Bach Gilbert ch. 6 (6th ed; pp 397-398 in 8th ed); ch.15 Additional Gilbert for germ line ch 19 (6th ed) and stem cells – from new edition 10/30/15 11/03/15 Treisman/ Bach Esteban Mazzoni Including paper discussion 11/06/15 Sevinc Ercan Including paper discussion Discussion Signaling in the context of development: Eye and germ line Hedgehog signaling and progressive differentiation Receptor tyrosine kinase signaling and photoreceptor identity Germ cells and gonadogenesis Stem cell - niche interaction SIGNALING, TRAFFICKING: HH, JAK/STAT, RTKs Discussion Genomes and development RNAi (si-, sh-, miRNA) and High Throughput Screens Functional genomics and proteomics Network analysis and integration of “omic” datasets Chemical genomics NYUMC NYUMC Genomes and development RNAi (si-, sh-, miRNA) and High Throughput Screens Functional genomics and proteomics Network analysis and integration of “omic” datasets Chemical genomics NYU NYUMC NYU 11/10/15 Jesús TorresVazquez/ Holger Knaut Gilbert ch. 13, 15 The cell biology of motility Types of migration: Amoeboid Fibroblast Cell sheets Types of migratory signals: Gradients/long-range Contact mediated/short-range Attractive, Repulsive ECM REMODELING, INTEGRINS GPCR SIGNALING IN MIGRATION Specific examples: Germ cells Border cells in Drosophila Neural crest Endothelial migration Axon guidance Migration and disease NYUMC 11/13/15 Torres-Vazquez/ Knaut Discussion NYUMC 6 11/17/15 Don Ryoo/ Ken Birnbaum Gilbert ch. 1, part of ch. 18, Gilbert ch.20 (PDF) Control of growth in development Animals Growth control at the cell, organ and organism level Cell survival, competition, death and proliferation TOR SIGNALING Plants Self-organization and patterning with indeterminate growth Stem cells and stem cell niches in plants and animals Plasticity of plant cells and totipotency NYU 11/20/15 11/24/15 Ryoo/Birnbaum Jane Hubbard Discussion Aging (one class, lecture and discussion together) INSULIN, NHR SIGNALING Metabolic influences on aging NYU NYUMC Neural patterning Anterio-posterior and Dorso-ventral patterning of neuroepithelium, Proliferation and migration Anterio-posterior and Dorso-ventral patterning of neuroepithelium Neuromeric development Stem cell and transit amplifying cell proliferation NOTCH SIGNALING Tangential versus Radial Migration in the PNS and CNS NYUMC Discussion NYUMC Including paper discussion Gilbert ch.18 11/27/15 12/1/15 NO CLASS Thanksgiving Gord Fishell/ Jean-Pierre SaintJeannet Gilbert ch. 12-13 12/4/15 Fishell/ Saint-Jeannet 12/11/15 FINAL PAPERS DUE 5PM 7 FACULTY DIRECTORY – DS I FALL 2015 Erika Bach Ken Birnbaum Lionel Christiaen Jeremy Dasen Claude Desplan Anna Di Gregorio Patrick Eichenberger Sevinc Ercan Adrian Erlebacher Gord Fishell Jane Hubbard Holger Knaut Ruth Lehmann Cindy Loomis Esteban Mazzoni Jeremy Nance Niels Ringstad Matt Rockman Don Ryoo Jean-Pierre Saint-Jeannet Stephen Small Nick Stavropoulos Jesús Torres-Vázquez Jessica Treisman erika.bach@nyu.edu ken.birnbaum@nyu.edu lc121@nyu.edu Jeremy.dasen@med.nyu.edu cd38@nyu.edu and2015@med.cornell.edu pe19@nyu.edu se71@nyu.edu adrian.erlebacher@med.nyu.edu Gordon.fishell@med.nyu.edu jane.hubbard@med.nyu.edu Holger.Knaut@med.nyu.edu Ruth.lehmann@med.nyu.edu Cynthia.loomis@nyumc.org eom204@nyu.edu Jeremy.nance@med.nyu.edu Niels.ringstad@med.nyu.edu Mrockman@nyu.edu HyungDon.Ryoo@nyumc.org jsj4@nyu.edu sjs1@nyu.edu Nicholas.Stavropoulos@nyumc.org Jesus.Torres-Vazquez@med.nyu.edu Jessica.treisman@med.nyu.edu Theresa Walton – COURSE ADMINISTRATOR Theresa.walton@med.nyu.edu