MCB 240

Spring 2009

Click on the date to view readings for each lecture.

Part I: Tom Cline
Part II: Barbara Meyer
Part III: Sharon Amacher

Part I: Advanced Genetic Analysis
Tom Cline

DATE TOPIC
Jan 20 Introduction to Drosophila and the origin of developmental genetics
Jan 22 Brute-force genetic screens in Drosophila
Jan 26 First Discussion: (a classic maternal-effect brute-force screen)
Jan 27 Sensitized genetic screens in Drosophila
Jan 29 Introduction to genetic mosaics in Drosophila
Feb 2 Second Discussion: (classic uses of mitotic recombination)
Feb 3 Mitotic recombination mosaics in Drosophila genetic screens
Feb 5 Enhancer traps as markers and mutagens in Drosophila
Feb 9 Third Discussion: (Etraps in the study of germline sex determination)
Feb 10 The GAL4 extension of Drosophila Etraps: driving tissue-specific gene expression
Feb 12 Extensions of the GAL4 extension (gal80 and others)
Feb 16 HOLIDAY, no discussion session. (A take-home problem set will be put on the course website by this day. Due Monday, February 23.)
Feb 17 Reverse genetics in Drosophila by targeted gene knockouts
Feb 19 Induced gene misexpression screens in Drosophila
Feb 23 No Discussion: Problem Set Due
JAN 20

Lecture #1: Introduction to Drosophila

  • Bridges, C.B. (1921) Triploid intersexes in Drosophila melanogaster. Science 54:252-254 [PDF]
    (a classic paper from the very beginning of the science of developmental genetics)
              .... and to see where this research led (and why you can't believe textbooks) :
  • Erickson, J.W. and Quintero, J.J. (2007) X chromosome dose, not the X:A ratio, signals sex in Drosophila. PLOS Biology 5:2821-2830 [PDF]

    The following are excellent general reviews of the techniques covered in this third of the course (a kind of "textbook", if you will).   You should read through these at least once, then consult them again as needed:

  • Rubin, G.M. (1988) (review) Drosophila melanogaster as an experimental organism. Science 240: 1453-1459
    (old, but still a good basic introduction) [PDF]
  • Matthews, K.A., Kaufman, T.C. and Gelbart, W.M., (2005) Research resources for Drosophila: the expanding universe. Nature Reviews Genetics 6: 179-193 [PDF]
  • St. Johnston, D. (2002) The art and design of genetic screens: Drosophila melanogaster. Nature Reviews Genetics 3: 176-188 [PDF]
  • Adams, M.D. and Sekelsky, J.J. (2002) From sequence to phenotype: reverse genetics in Drosophila melanogaster. Nature Reviews Genetics 3: 189-198 [PDF]
  • Venken, K.J.T. and Bellen, H.J. (2005) Transgenesis upgrades for Drosophila melanogaster. Nature Reviews Genetics 6: 167-178 [PDF]
JAN 22

Lecture #2: Brute-force genetic screens in Drosophila

  • Judd, B.H., Shen, M.W. and Kaufman, T.C. (1971) The anatomy and function of a segment of the X chromosome of Drosophila melanogaster. Genetics 71:139-156 [PDF]
  • Nüsslein-Volhard, C. and Wieschaus, E. (1980) Mutations affecting segment number and polarity in Drosophila. Nature 287: 795-801 [PDF]
Discussion (JAN 26)

First Discussion: (a classic maternal-effect brute-force screen)

Schüpbach, T. and Wieschaus, E. (1989) Female sterile mutations on the second chromosome of Drosophila melanogaster. I. Maternal effect mutations. Genetics 121:101-117 [PDF]
JAN 27

Lecture #3: Sensitized genetic screens in Drosophila

  • Simon, M.A., Bowtell, D.D.L., Dodson, G.S., Laverty, T.R. and Rubin, G.M. (1991) Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase. Cell 67: 701-716. [PDF]
  • Stewart, R.A., Li, D-M, Huang, H., and Xu, T. (2003) A genetic screen for modifiers of the lats tumor suppressor gene identifies C-terminal Src kinase as a regulator of cell proliferation in Drosophila. Oncogene 22: 6436-6444 [PDF]
JAN 29 Lecture #4: Introduction to genetic mosaics in Drosophila

  • Blair, S.S. (2003) Genetic mosaic techniques for studying Drosophila development. Development 130: 5065-72. [PDF]

Discussion
(FEB 2) 		Second Discussion: (classic uses of mitotic recombination)
  • Morata, G. and Lawrence, P.A. (1977) Control of compartment development by the engrailed gene in Drosophila. Nature 255:614-617 [PDF]
  • Simpson, P. (1979) Parameters of cell competition in the compartments of the wing disc of Drosophila. Develop. Biol. 69: 182-193 [PDF]

    ... and to see (literally see with your eyes) where compartment studies led:

  • Nellen, D., Burke, R., Struhl, G., and Basler, K. (1996) Direct and Long-Range Action of a DPP Morphogen Gradient. Cell 85:357-368 [PDF]
    [Just skim this paper (intro & discsn mainly; these techniques will come later)]
FEB 3

Lecture #5: Mitotic recombination mosaics in Drosophila genetic screens

  • Perrimon, N., Engstrom, L. and Mahowald, A.P. (1989) Zygotic lethals with specific maternal effect phenotypes in Drosophila melanogaster. I. Loci on the X chromosome. Genetics 121:333-352 [PDF]
  • Xu, T., Wang, W., Zhang, S., Stewart, R.A. and Yu, W. (1995) Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development 121: 1053-1063 [PDF]
FEB 5 Lecture #6: Enhancer traps as markers and mutagens in Drosophila
  • Bier, E., et 12 al . (1989) Searching for pattern and mutation in the Drosophila genome with a P-lacZ vector. Genes & Develop. 3: 1273-1287 [PDF]
  • Stempfl, T. et al. (2002) Identification of circadian-clock-regulated enhancers and genes of Drosophila melanogaster by transposon mobilization and luciferase reporting of cyclical gene expression. Genetics 160:571-93 [PDF]

Discussion (FEB 9)

Third Discussion: (Etraps in the study of germline sex determination)
  • Heller, A., and Steinmann-Zwicky, M. (1998) In Drosophila, female gonadal cells repress male-specific gene expression in XX germ cells. Mechanisms of Development 73: 203-209 [PDF]
  • Janzer, B. and Steinmann-Zwicky, M. (2001) Cell-autonomous and somatic signals control sex-specific gene expression in XY germ cells of Drosophila. Mechanisms of Development 100: 3-13 [PDF]

    And for a review on germline sex determination for background (don't have to read):     

  • Casper, A. and VanDoren, M. (2006) The control of sexual identity in the Drosophila germline. Development 133: 2783-2791 [PDF]

FEB 10 Lecture #7: The GAL4 extension of Drosophila Etraps: driving tissue-specific gene expression
  • Halder, G., Callaerts, P. and Gehring, W.J. (1995) Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science 267: 1788-1792 [PDF]
  • Duffy, J.B., Harrison, D.A., and Perrimon, N. (1998) Identifying loci required for follicular patterning using directed mosaics. Development 125: 2263-2271 [PDF]
FEB 12

Lecture #8: Extensions of the GAL4 extension (gal80 and others)

  • Basler, K. and Struhl, G. (1994) Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein. Nature 368:208-214 [PDF]
  • McGuire, S.E., Le, P.T., Osborn, A.J., Matsumoto, K., and Davis, R.L. (2003) Spatiotemporal rescue of memory dysfunction in Drosophila. Science 302:1765-245 [PDF]
  • Suster, M.L., Seugnet, L., Bate, M. and Sokolowski, M.B. (2004) Refining GAL4-driven transgene expression in Drosophila with a GAL80 enhancer-trap. Genesis 39: 240-245 [PDF]

Discussion (FEB 16)

HOLIDAY, no discussion section. However, a take-home problem set will be put on the course website by this day.   Due Monday, Feb. 23.

FEB 17

Lecture #9: Reverse genetics in Drosophila by targeted gene knockouts

  • Rong, S.Y., ....(& many) ... and Golic, K.G. (2002) Targeted mutagenesis by homologous recombination in D. melanogaster. Genes and Development 16: 1568-1581. [PDF]
  • Gong, W.J. and Golic, K.G. (2003) Ends-out, or replacement, gene targeting in Drosophila. Proc. Nat. Acad. Sci. USA 100: 2556-2561 [PDF]
  • Xie, H.B. and Golic, K.G. (2004) Gene deletions by ends-in targeting in Drosophila melanogaster. Genetics 168: 1477-1489 [PDF]
FEB 19

Lecture #10: Induced gene misexpression screens in Drosophila

  • Rørth, P. ...(& many)...and Cohen, S.M. (1998) Systematic gain-of-function genetics in Drosophila. Development 125: 1049-1057 [PDF]
  • Schultz, C. ... (& many)... and Fuller, M.T. (2004) A misexpression screen reveals effects of bag-of-marbles and TGF β class signaling on the Drosophila male germ-line stem cell lineage. Genetics 167:707-723 [PDF]

Discussion
(FEB 23)

No discussion. Second Problem Set Due

Part II:
Barbara Meyer

DATE TOPIC
Feb 24 Hermaphrodite Genetics: Introduction to C. elegans
Feb 26 Building a Genetic Pathway: Cell Death
Mar 2 Discussion
Mar 3 Genetic Mosaic Analysis: Cell Signaling
Mar 5 Convergence of Signaling Pathways to Specify Cell Fate
Mar 9 Discussion
Mar 10

Cell Signaling continued

Mar 12 RNA Interference, miRNAs, Temporal Control of Development
Mar 16 Discussion
Mar 17 Genomics Approaches
Mar 19

Genetic Specification of Life Span

Mar 23

Problem Set available today and due 6 April at 5PM in Meyer mailbox in Koshland Hall

Mar 30 Stem Cell Maintenance and Meiosis (lecture, not discussion)
Mar 31 Germline X-Chromosome Silencing and Somatic X-Chromosome Dosage Compensation
Apr 2 No lecture
FEB 24

Hermaphrodite Genetics: Introduction to C. elegans

* indicates Required Reading

The paper immediately below is the first written on C. elegans genetics, establishing the nematode as a model genetic organism.

*Brenner, S. (1974) The genetics of Caenorhabditis elegans. Genetics 77, 71-94. [PDF]

*Brenner, S. (2003) (Nobel Lecture)  Nature's gift to science. ChembioChem 4, 683-687. [PDF]

This paper is a general reference that lists all websites and resources available for comprehensive information and analysis of C. elegans.

Antoshechkin, I. and Sternberg, P.W. (2007) The versatile worm: genetic and genomic resources for Caenorhabditis elegans research. Nat. Rev. Genet. 8, 518-532. [PDF]

Use the massive review below as a reference to look up aspects of C. elegans genetics as you need them. A quick look through will familiarize you with the contents, so you know the topics it will clarify for you.

Fay, D. (2005) Genetic Mapping and manipulation. WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.7.1, http://www.wormbook.org

FEB 26

Building a Genetic Pathway: Cell Death

*Hengartner, M., Ellis R., and Horvitz, H. R. (1992) C. elegans gene ced-9 protects cells from programmed cell death. Nature 356, 494-499. [PDF]

*Peden et al . (2007) Control of sex-specific apoptosis in C. elegans by the BarH homeodomain protein CEH-30 and the transcriptional repressor UNC-27 / Groucho. Genes Dev. 21, 3195-3207. [PDF]
Supplementary Material [PDF]

*Review
Horvitz, H. R. (2003) (Nobel lecture) Worms, Life and Death.   ChemBioChem 4, 697-711. [PDF]
Discussion (MAR 2)

*Conradt, B. and Horvitz H. R.   (1999) The TRA-1A sex determination protein of C. elegans regulates sexually dimorphic cell deaths by repressing the egl-1 death activator gene. Cell 98, 317-327. [PDF]
MAR 3

Genetic Mosaic Analysis: Cell Signaling

*Seydoux, G. and Greenwald, I. (1989) Cell autonomy of lin-12 function in a cell fate decision in C. elegans. Cell 57, 1237-1245. [PDF]

*Herman, R.K., Hedgecok, E.M. (1990) Limitation of the size of the vulval primordium of Caenorhabditis elegans by lin-15 expression in surrounding hypodermis. Nature 348, 169-171. [PDF]

Review
Jochem, J. and Herman, R. K. (2003) Investigating C. elegans development through mosaic analysis. Development 130, 4761-4768. [PDF]

MAR 5

Convergence of Signaling Pathways to Specify Cell Fate

*Chen, N. and Greenwald, I. (2004) The lateral signal for LIN-12/Notch in C. elegans vulval development comprises redundant secreted and transmembrane DSL proteins.  Dev. Cell 6, 183-192. [PDF]

*Yoo, A., Bais, C., and Greenwald, I. (2004) Crosstalk between the EGFR and LIN-12/Notch pathways in C. elegans vulval development.   Science 303, 663-666. [PDF]
Supplementary Information [PDF]

Review as a reference guide on vulval development

Sternberg, P.W. (2005)   Vulval development. WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.6.1,
http://www.wormbook.org. [PDF]

Discussion
(MAR 9) 		*Myers, T. and Greenwald, I. (2005)  lin-35 RB acts in the major hypodermis to oppose RAS-mediated vulval induction in C. elegans.   Dev. Cell 8, 117-123. [PDF]

*Yoo, A. and Greenwald, I. (2005) LIN-12/Notch activation leas to microRNA-mediated down-regulation of vav in C. elegans.   Science 310, 1330-1333. [PDF]
Supplementary Information [PDF]
MAR 10

Cell Signaling continued

MAR 12 RNA Interference, miRNAs, Temporal Control of Development

*Fire, A. et al. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.  Nature 391, 806-811. [PDF]

*Reinhart, B. et al. (2000) The 21-nucleotide let-7 RNA regulates developmental timing in C. elegans.  Nature 403, 901-906. [PDF]

Discussion (MAR 16)

*Winston, W.M., Molodowitch, C., and Hunter C. P. (2002) Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science 295, 2456-2459. [PDF]

*Ao, W. et al. (2004) Environmentally induced foregut remodeling by PHA-4 / FoxA and DAF-12/NHR. Science 305, 1743-1746. [PDF]

MAR 17

Genomics Approaches
*Blumenthal T. et al. (2002) A global analysis of Caenorhabditis elegans operons. Nature 417, 851-854. [PDF]

*Kamath R. S. et al. (2003) Systematic functional analysis of the Caenorhabditis elegans genome using RNAi.  Nature 421, 231-237. [PDF]

MAR 19

Genetic Specification of Life Span

*Pinkston, J. M. et al. (2006) Mutations that increase the life span of C. elegans inhibit tumor growth.  Science 313, 971-975. [PDF]

*Arantes-Olliveira, N. et al. (2002) Regulation of life-span by germ-line stem cells in Caenorhabditis elegans. Science 295, 502-505. [PDF]

Review
Kenyon, C. (2005)   The Plasticity of Aging: Insights from Long-Lived Mutants. Cell 120, 449-460. [PDF]

MAR 23 Problem Set available today and due 6 April at 5PM in Meyer mailbox in Koshland Hall
MAR 30 Stem Cell Maintenance and Meiosis (lecture, not discussion)

*Hansen, D. et al. (2004) Control of the proliferation versus meiotic developmental decision in the C. elegans germline through regulation of GLD-1 protein accumulation. Development 131, 93-104. [PDF]
MAR 31

Germline X-Chromosome Silencing and Somatic X-Chromosome Dosage Compensation

*Fong Y. et al. (2002) Regulation of the different chromatin states of autosomes an X chromosomes in the germ line of C. elegans.   Science 296, 2235-2238. [PDF]
Link to Supplemental Material

*Jans, J. Gladden, J.M., Ralston, E.J., Pickle, C.S., Michel, A.H., Pferdehirt, R.R., Eisen, M.B., Meyer, B.J. (2009)   A condensin-like dosage compensation complex acts at a distance to control expression throughout the genome. Genes & Dev. 23(5). [PDF]
Supplemental material [PDF]

APR 2

No lecture

Part III: Vertebrate Developmental Genetics
Sharon Amacher

 

Updated March 9, 2009
http://mcb.berkeley.edu/courses/mcb240/Readings.htm