Home

Genetics

Segmentation

Courses

Protocols

Publications

People

Transgenics

Dept.

1  |  2  |  3  |  4  |  5  |  6  |  7  |  8  |  9  |  10  |  11  |  12  |  13  |  14

Gene 523: Embryonic Patterning

    This course will focus on our current understanding of patterning mechanisms in animal development. Models and theory will be considered, in addition to experimental analysis and the identification of patterning molecules.

    Primary literature will be assigned for the students to read and discuss in each class. Students will be graded on their contributions to discussions and on a written assignment. It is recommended that students have completed the core courses in the Department of Genetics, GENE 500 and GENE 504, prior to taking this course or receive the permission of the instructor.

    Plagiarism is a serious breach of academic integrity and will be treated as such. I will be testing all written materials submitted by students for plagiarism. Read and understand the Case Definitions and Policies Regarding Plagiarism and understand that the consequences of commiting plagiarism are expulsion from the University.

    Classes are scheduled for Wednesdays at 1 PM in BRB 732.

---

Embryology Learning Resources There is a written assignment. Read comments on the class from 2005, 2003 and 2001. Introduction to Embryology (The FAQs) Wolpert (1996) One hundred years of positional information. Trends Genet 12, 359-64.

---

CLASSES

1. Morphogen Gradients: Is the bicoid gradient established by diffusion, source and sink? (Wednesday, Sept 5, 2007)

Classic papers in the field

Required Reading

• Introduction:
  • Fly Development
  • Gilbert: Bicoid
• Review: Kerszberg and Wolpert (2007) Specifying positional information in the embryo: looking beyond morphogens. Cell 130(2):205-9.
• Crick F (1970) Diffusion in embryogenesis. Nature 225(5231):420-2
• Gregor et al. (2005) Diffusion and scaling during early embryonic pattern formation. PNAS 102(51):18403-7.
• Gregor et al. (2007) Stability and nuclear dynamics of the bicoid morphogen gradient. Cell 130(1):141-52.
• Supplement
• Supplemental Movie
• Gregor et al. (2007) Probing the limits to positional information. Cell 130(1):153-64.
• Questions

2. Morphogen Gradients: How is morphogen concentration interpreted? (Wednesday Sept 12, 2007)

Classic papers in the field

Required Reading

• Introduction:
  • Mesoderm Induction
  • Xenopus Development
  • Jeff Hardin: Xenopus Gastrulation
• Review: Gurdon and Bourillot (2001) Morphogen Gradient Interpretation. Nature 413, 797-803.
• Dyson and Gurdon (1998) The interpretation of position in a morphogen gradient as revealed by occupancy of activin receptors. Cell 93, 557-568.
• Jullien and Gurdon (2005) Morphogen gradient interpretation by a regulated trafficking step during ligand-receptor transduction. Genes Dev 19(22):2682-94
• Questions

3. Making Boundaries and Keeping them Straight (Wednesday Sept 19, 2007)

Classic papers in the field

Required Reading

• Introduction:
  • Boundaries
  • Gilbert: Differential Adhesion
  • Differential Adhesion
  • Review: Tepass et al., (2002) Cell sorting in animal development: signalling and adhesive mechanisms in the formation of tissue boundaries. Current Opinion in Geneteics & Development 12, 572-582.
  • Crick, F. H., and Lawrence, P. A. (1975). Compartments and polyclones in insect development. Science 189, 340-347.
• Xu, et al. (1999) In vivo cell sorting in complementary segmental domains mediated by Eph receptors and ephrins. Nature 399, 267-271.
• Mellitzer, et al. (1999) Eph receptors and ephrins restrict cell intermingling and communication. Nature 400, 77-81.
• Cooke et al., (2005) EphA4 is required for cell adhesion and rhombomere-boundary formation in the zebrafish. Curr Biol 15(6):536-42
• Questions

4. Morphogen Spread: Cytonemes, Endocytosis or Diffusion? (Wednesday, Sept 26, 2007)

Required Reading

• Review: Zhu, A. J., and Scott, M. P. (2004) Incredible journey: how do developmental signals travel through tissue? Genes Dev 18, 2985-97.
• Ramirez-Weber and Kornberg (1999) Cytonemes: cellular processes that project to the principal signaling center in Drosophila imaginal discs. Cell 97, 599-607.
• Entchev et al., (2000) Gradient formation of the TGF-beta homolog Dpp. Cell 103,981-991.
• Belenkaya et al., (2004) Drosophila Dpp morphogen movement is independent of dynamin-mediated endocytosis but regulated by the glypican members of heparan sulfate proteoglycans. Cell 119(2):231-44.
• Questions

5. Setting positional values by time exposed to a morphogen. (Wednesday, Oct 3, 2007)

Classic papers in the field

Required Reading

• Introduction
  • Limb Development (.doc file)
• Summerbell, et al. (1973) Positional information in chick limb morphogenesis. Nature 244, 492-6.
• Pfeiffer et al., (2000) The progeny of wingless-expressing cells deliver the signal at a distance in Drosophila embryos. Current Biology 10, 321-324.
• Ahn and Joyner (2004) Dynamic changes in the response of cells to positive hedgehog signaling during mouse limb patterning. Cell 118(4):505-16.
• Harfe et al., (2004) Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identities. Cell 118(4):517-28.
• Questions

6. Cellular state and the epigenetic code. (Wednesday, Oct 10, 2007)

Required Reading

• Introduction:
  • The developmental landscape, canalization, cellular state and the epigenetic code
• Review: Jaenisch et al., (2005) Nuclear cloning, epigenetic reprogramming and cellular differentiation. Novartis Found Symp 265:107-18
• Eggan et al., (2004) Mice cloned from olfactory sensory neurons. Nature 428(6978):44-9
• Mikkelsen et al., (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448(7153):553-60
• Wernig et al., (2007) In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448(7151):318-24
• Questions

7. Lateral Inhibition (Wednesday, Oct 17, 2007)

• Introduction:
  • Lateral Inhibition
  • C elegans
  • Gilbert: C elegans Vulva Induction
  • Gilbert: Notch Signalling
• Review: Perrimon and Duffy (1998) Developmental biology. Sending all the right signals. Nature 396(6706): 18-9
• Heitzler and Simpson (1991) The choice of cell fate in the epidermis of Drosophila. Cell 64(6): 1083-92
• De Joussineau et al., (2003) Delta-promoted filopodia mediate long-range lateral inhibition in Drosophila. Nature 426(6966): 555-9
• Wasserman and Freeman (1998) An autoregulatory cascade of EGF receptor signaling patterns the Drosophila egg. Cell 95(3): 355-64
• Nakamura and Matsuno (2003) Species-specific activation of EGF receptor signaling underlies evolutionary diversity in the dorsal appendage number of the genus Drosophila eggshells. Mech Dev 120(8): 897-907.

8. Branching Morphogenesis (Wednesday Oct 24, 2007).

• Introduction:
  • Gilbert 6th ED: Induction of Lungs
  • Gilbert 7th ED: Lung Branching Morphogenesis
  • Lungs
• Review: Lu et al., (2006) Comparative mechanisms of branching morphogenesis in diverse systems. J Mammary Gland Biol Neoplasia 11(3-4):213-28
• Sutherland et al., (1996) branchless encodes a Drosophila FGF homolog that controls tracheal cell migration and the pattern of branching. Cell 87, 1091-1101
• Cabernard and Affolter (2005) Distinct roles for two receptor tyrosine kinases in epithelial branching morphogenesis in Drosophila. Dev Cell 9(6):831-42
• Ghabrial and Krasnow (2006) Social interactions among epithelial cells during tracheal branching morphogenesis. Nature 441(7094):746-9

9. Brian Dudley: Planar Cell Polarity (Wednesday October 31, 2007)

Classic Paper (not required; handout):

• Vinson and Adler (1987).  Directional non-cell autonomy and the transmission of polarity information by the frizzled gene of Drosophila.  Nature 329: 549-551.

Required Reading:

• Review:  Zallen (2007).  Planar polarity and tissue morphogenesis.  Cell 129: 1051-1063.
• Strutt (2001).  Asymetric localization of Frizzled and the establishment of cell polarity in the Drosophila wing.  Molecular Cell 7: 367-375.
• Tree et al (2002).  Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling.  Cell 109: 371-381.
• Guo et al (2004).  Frizzled6 controls hair patterning in mice. Proc Natl Acad Sci USA 101: 9277-9281.
• Questions

10. Thu Tran: Segmentation Clock (Wednesday November 7, 2007)

Classic Paper:

• Cooke and Zeeman (1976)  A clock and wavefront model for control of the number of repeated structures during animal morphogenesis. J Theor. Biol. 58: 455-476.

Required Reading:

• Review: Cinquin (2007) Understanding the somitogenesis clock: what's missing? Mech Dev 124(7-8):501-17
• Aulehla et al. (2003) Wnt3a plays a major role in the segmentation clock controlling somitogenesis. Dev Cell 4(3):395-406
• Bessho et al., (2003) Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock. Genes Dev 17(12):1451-6
• Wahl et al., (2007) FGF signaling acts upstream of the NOTCH and WNT signaling pathways to control segmentation clock oscillations in mouse somitogenesis. Development 134(22):4033-41

11. Yiwei Wang: Left-Right Asymmetry (Wednesday November 14, 2007)

• Classsic paper: Brown and Wolpert. (1990) The development of handedness in left/right asymmetry. Development 109(1):1-9
• Review paper: Hamada et al. (2002) Establishment of vertebrate left-right asymmetry. Nat Rev Genet 3(2):103-13
• Nonaka et al. (1998) Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. Cell 95(6):829-37
• Nonaka et al. (2002) Determination of left-right patterning of the mouse embryo by artificial nodal flow. Nature 418(6893): 96-9
• supplement online: http://www.nature.com/nature/journal/v418/n6893/suppinfo/nature00849.html
• McGrath et al. (2003) Two Populations of Node Monocilia Initiate Left-Right Asymmetry in the Mouse. Cell 114(1):61-73
• Questions

12. Thanksgiving (Wednesday November 21, 2007)


13. Reaction Diffusion (Wednesday November 28, 2007)

Classic Papers:

• Gierer A, Meinhardt H. (1972) A theory of biological pattern formation. Kybernetik 12(1):30-9
• Newman and Frisch (1979) Dynamics of skeletal pattern formation in developing chick limb. Science 205: 662-8.

Required Reading:

• Introduction: Reaction-Diffusion
• Review: Maini (2003) How the mouse got its stripes. PNAS 100, 9656-9657.
• Suzuki et al., Traveling stripes on the skin of a mutant mouse. PNAS 100, 9680-9685.
• Maderspacher and Nusslein-Volhard (2003) Formation of the adult pigment pattern in zebrafish requires leopard and obelix dependent cell interactions. Development 130, 3447-3457.
• Kessler and Werner (2003) Self-organization of sorted patterned ground. Science 299, 380-383.
• Theraulaz et al., (2002) Spatial patterns in ant colonies PNAS 99, 9645-9649.