Bio 488: Selected Topics in Development
Professor Elena Casey
Rm 438 Reiss Science Building
Wednesday 2:50-4:55
Goals: To learn and discuss some of the major topics in human embryonic development.
How multicellular animals develop has long been a central area of study in the biological sciences.
Technological innovations in recent years have stimulated a virtual explosion of new information
and conceptual breakthroughs, providing molecular mechanisms for fundamental developmental
processes. The objective of this course is to introduce you to these concept and techniques by
reading and discussing primary research literature in developmental biology. We will focus on the
genetic regulation of developmental pathways and processes. However, organismal, cellular, and
biochemical perspectives will also be discussed.
Rather than exploring a wide spectrum of developmental systems and developmental
processes, this course is designed to examine selected topics in pattern formation and cell fate
specification in considerable depth. We will also discuss how some of this research is portrayed in
the press and examine some of the more controversial aspects of development and discuss the
ethics of this research. However, this course emphasizes research articles and reviews, providing
a particularly detailed study of specific processes in vertebrate development. With this approach,
the goal is to encourage use of resources that will allow students to learn not only important
developmental facts, but also how to think about underlying mechanisms that make the processes
dynamic and how to critically read current literature. Previous course work in cell and/or
developmental biology would be useful.
Format:
Each class period we will first discuss a review paper. To do this, every person in the class will
present the answer to a question provided the previous week. Part of your grade is dependent on
the lucidity and precision of your answers each week. Next we will discuss ethical issues and/or
representations of this subject in the media. Finally, a student will do a powerpoint presentation of
the research paper. This presentation must be discussed on the Monday before class with Dr.
Casey and the completed version must be sent to her via email the night before.
Textbooks and reading:
The review and research papers will be handed out in class the week prior to discussion. They will
also be posted on blackboard
Required book:
Gilbert, Tyler, and Zacki. Bioethics and the new embryology [BNE]
Reference text on reserve in Science Library:
Gilbert, Scott F. Developmental Biology 6th edition [DB]
Also available on line at:
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=dbio.TOC&depth=2
Grading:
20%
25%
20%
10%
25%
in class participation (including answering provided questions)
powerpoint presentation
take home midterm
written problem sets
take home final
1
Presentation assignment: This is closer to a journal club!
You will be given a topic and one paper on which you will lead a discussion. Give an introduction of
the subject…[e.g. Development of the olfactory system involves…This subject is of particular
interest because………. The researchers address this problem by using this approach……. ]
Then systematically go through each figure. You must show the figure by powerpoint or some other
equivalent program. You may ask people for their opinions to describe a figure but be ready to
answer detailed questions on the paper.
Date Tenative Topics_______________ __________
1/18/05
- Discuss syllabus
- Assign presentation topics
- Discuss early human development and research paper
- Ethics- when does life begin?
Reading assignment:
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Chapters 1 and 2 [BNE]
Chapter 3 (pgs 49-64) [BNE]
For more detailed information on mammalian development (NOT required):
o Early human embryo development [Gilbert]: pgs 354-364 - link on Blackboard
o Glossary [handout] - Early embryonic development
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Lin, Y et al. A Hyaluronidase Activity of the Sperm Plasma Membrane Protein PH-20 Enables
Sperm to Penetrate the Cumulus Cell Layer Surrounding the Egg. The Journal of Cell Biology
1994, Vol 125, (5): 1157-1163.
Sample papers are listed for each topic below. Specific assignments will be given the week
before class. Prior to your presentation you should go over the figures with Dr. Casey
1/25/05
Assisted reproduction [genomic imprinting]
Reading assignment
 [BNE] pages 64-79 - Ethics of ART
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Thompson JR, Williams CJ. Genomic imprinting and assisted reproductive technology:
connections and potential risks. Semin Reprod Med. 2005 Aug;23(3):285-95.
Paria BC, Dey SK. Preimplantation embryo development in vitro: cooperative interactions
among embryos and role of growth factors. Proc Natl Acad Sci U S A. 1990 Jun;87(12):475660.
Li et al. IVF results in de novo DNA methylation and histone methylation at an Igf2-H19
imprinting epigenetic switch. Molecular Human Reproduction 2005 Vol.11, No.9 pp. 631–640.
2
2/01/05
Preimplantation genetic diagnosis [Sex determination]
Reading assignment
 [BNE Chapter 5 and 6] Ethics of determining sex of embryo
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Braude, P., Pickering, S., Flinter, F., and Ogilvie, C. M. Preimplantation genetic diagnosis. Nat
Rev Genet 2002 (3), 941-955.
Jennifer Brennan, Blanche Capel. One tissue, two fates: Molecular genetic events that underlie
testis versus ovary development. Nature Reviews Genetics, Vol. 5, 509-521, July 2004.
Cui S, Ross A, Stallings N, Parker KL, Capel B, Quaggin SE. Disrupted gonadogenesis and
male-to-female sex reversal in Pod1 knockout mice. Development. 2004 Aug;131(16):4095105.
Chaboissier MC, Kobayashi A, Vidal VI, Lutzkendorf S, van de Kant HJ, Wegner M, de Rooij
DG, Behringer RR, Schedl A. Functional analysis of Sox8 and Sox9 during sex determination in
the mouse. Development. 2004 May;131(9):1891-901. Epub 2004 Mar 31.
2/08/05
Stem cells [fate determination and organ building]
Reading assignment
 [BNE] Chapter 9 and 10
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Daley, G. Q. (2002) Prospects for stem cell therapeutics: myths and medicines. Curr Opin
Genet Dev 12, 607-613.
Amato MA, Arnault E, Perron M. Retinal stem cells in vertebrates: parallels and divergences.
Int J Dev Biol. 2004;48(8-9):993-1001.
Davor Solter. Mammalian Cloning: Advances and Limitations. Nature Reviews Genetics 1, 199
- 207 (01 Dec 2000) Review Article
Pera MF, Trounson AO. Human embryonic stem cells: prospects for development.
Development. 2004 Nov;131(22):5515-25.
Giarratana MC, Kobari L, Lapillonne H, Chalmers D, Kiger L, Cynober T, Marden MC, Wajcman
H, Douay L.Ex vivo generation of fully mature human red blood cells from hematopoietic stem
cells. Nat Biotechnol. 2004 Dec 26; *
Plachta N, Bibel M, Tucker KL, Barde YA. Developmental potential of defined neural progenitors
derived from mouse embryonic stem cells. Development. 2004 Nov;131(21):5449-56.
Ferron S, Mira H, Franco S, Cano-Jaimez M, Bellmunt E, Ramirez C, Farinas I, Blasco MA.
Telomere shortening and chromosomal instability abrogates proliferation of adult but not
embryonic neural stem cells. Development. 2004 Aug;131(16):4059-70.
Wurmser AE, Nakashima K, Summers RG, Toni N, D'Amour KA, Lie DC, Gage FH. Cell fusionindependent differentiation of neural stem cells to the endothelial lineage. Nature. 2004 Jul
15;430(6997):350-6.
3
2/15/05
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Weinstein, BM. Plumbing the mysteries of vascular development using the zebrafish.
Semin Cell Dev Biol. 2002 Dec;13(6):515-22.
Peter Carmeliet. Mechanisms of angiogenesis and arteriogenesis. Nature Medicine 6, 389 -395
(01 Apr 2000) Review Article
Nakamura K, Yamamoto A, Kamishohara M, Takahashi K, Taguchi E, Miura T, Kubo K,
Shibuya M, Isoe T. KRN633: A selective inhibitor of vascular endothelial growth factor receptor2 tyrosine kinase that suppresses tumor angiogenesis and growth. Mol Cancer Ther. 2004
Dec;3(12):1639-49.
Dooley KA, Davidson AJ, Zon LI. Zebrafish scl functions independently in hematopoietic and
endothelial development. Dev Biol. 2005 Jan 15;277(2):522-36.
Torres-Vazquez J, Gitler AD, Fraser SD, Berk JD, Van N Pham, Fishman MC, Childs S, Epstein
JA, Weinstein BM. Semaphorin-plexin signaling guides patterning of the developing vasculature.
Dev Cell. 2004 Jul;7(1):117-23.
Kertesz N, Wu J, Chen TH, Sucov HM, Wu H. The role of erythropoietin in regulating
angiogenesis. Dev Biol. 2004 Dec 1;276(1):101-10.
Gu C, Rodriguez ER, Reimert DV, Shu T, Fritzsch B, Richards LJ, Kolodkin AL, Ginty DD.
Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular
development. Dev Cell. 2003 Jul;5(1):45-57.
2/22/05
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Arteries and Veins [mesodermal derivative – relation to cancer]
Pancreas formation [Induction and endoderm]
Lammert E, Cleaver O, Melton D. Role of endothelial cells in early pancreas and liver
development. Mech Dev. 2003 Jan;120(1):59-64. Review.
Kumar M, Jordan N, Melton D, Grapin-Botton A. Signals from lateral plate mesoderm instruct
endoderm toward a pancreatic fate. Dev Biol. 2003 Jul 1;259(1):109-22.
Lammert E, Cleaver O, Melton D. Induction of pancreatic differentiation by signals from blood
vessels. Science. 2001 Oct 19;294(5542):564-7.
Zaret KS. Hepatocyte differentiation: from the endoderm and beyond. Curr Opin Genet Dev.
2001 Oct;11(5):568-74. Review.
Take home midterm receive 2/22– due 2/27 by noon
3/01/05
Cloning (everyone will participate in this discussion)
3/08/05
SPRING BREAK
3/15/05
Neurogenesis
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Gotz M, Huttner WB. The cell biology of neurogenesis. Nat Rev Mol Cell Biol. 2005
Oct;6(10):777-88. Review.
Bally-Cuif L, Hammerschmidt M. Induction and patterning of neuronal development, and
its connection to cell cycle control. Curr Opin Neurobiol. 2003 Feb;13(1):16-25.
Review.
Reichert H. Conserved genetic mechanisms for embryonic brain patterning. Int J Dev
Biol. 2002 Jan;46(1):81-7. Review.
4
3/22/05
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Andrew O. M. Wilkie, Gillian M. Morriss-Kay. Genetics of Cranial facial development and
malformation. Nature Reviews Genetics2, 458 - 468 (01 Jun 2001) Review Article
Le Douarin NM, Creuzet S, Couly G, Dupin E Neural crest cell plasticity and its limits.
Development. 2004 Oct;131(19):4637-50. Review.
Sabine P. Cordes. Molecular genetics of cranial nerve development in mouse. Nature Reviews
Neuroscience2, 611 - 623 (01 Sep 2001) Review Article -213/
3/29/05
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Neural crest- PNS development
Cerebral Cortex
Spassky N, Merkle FT, Flames N, Tramontin AD, Garcia-Verdugo JM, Alvarez-Buylla A.Adult
ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis. J
Neurosci. 2005 Jan 5;25(1):10-8.
Ma V, Lim DA, Dahmane N, Sanchez P, Brionne TC, Herzberg CD, Gitton Y, Carleton A,
Alvarez-Buylla A, Altaba AR. Sonic hedgehog controls stem cell behavior in the postnatal
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and adult brain. Development. 2005 Jan;132(2):335-44. Epub 2004 Dec 16.
Cajal nobel lecture -http://nobelprize.org/medicine/laureates/1906/cajal-lecture.pdf
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Caviness VS Jr, Sidman RL. Time of origin or corresponding cell classes in the cerebral cortex
of normal and reeler mutant mice: an autoradiographic analysis. J Comp Neurol. 1973 Mar
15;148(2):141-51.
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Rakic P, Sidman RL. Weaver mutant mouse cerebellum: defective neuronal migration
secondary to abnormality of Bergmann glia. Proc Natl Acad Sci U S A. 1973 Jan;70(1):2404.
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O'Rourke NA, Chenn A, McConnell SK. Postmitotic neurons migrate tangentially in the cortical
ventricular zone. Development. 1997 Mar;124(5):997-1005.
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D'Arcangelo G, Miao GG, Chen SC, Soares HD, Morgan JI, Curran T. A protein related to
extracellular matrix proteins deleted in the mouse mutant reeler. Nature. 1995 Apr
20;374(6524):719-23.
4/05/05 EYE – retinogenesis
 Saha MS, Servetnick M, Grainger RM. Vertebrate eye development. Curr Opin Genet Dev.
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1992 Aug;2(4):582-8. Review.
Chiang C, Litingtung Y, Lee E, Young KE, Corden JL, Westphal H, Beachy PA. Cyclopia and
defective axial patterning in mice lacking Sonic hedgehog gene function. Nature. 1996 Oct
3;383(6599):407-13.
Harris WA, Messersmith SL. Two cellular inductions involved in photoreceptor determination in
the Xenopus retina. Neuron. 1992 Aug;9(2):357-72.
5
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Pittack C, Grunwald GB, Reh TA. Fibroblast growth factors are necessary for neural retina but
not pigmented epithelium differentiation in chick embryos. Development. 1997 Feb;124(4):80516.
4/12/05
Axon Guidance
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Dickson BJ. Molecular mechanisms of axon guidance. Science. 2002 Dec
6;298(5600):1959-64. Review. Erratum in: Science. 2003 Jan 24;299(5606):515.
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Causeret, F. et al. 2002 Slit antagonizes netrin-1 attractive effects during the migration
of inferior olivary neurons, Developmental Biology 246, 429-440
4/19/05
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Hinck L. The versatile roles of "axon guidance" cues in tissue morphogenesis.
Dev Cell. 2004 Dec;7 (6):783-93.
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Affolter M, Bellusci S, Itoh N, Shilo B, Thiery JP, Werb Z. Tube or not tube: remodeling epithelial
tissues by branching morphogenesis. Dev Cell. 2003 Jan;4(1):11-8. Review. **
4/26/5
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Lung development
Evolution
Hamrick MW. Development and evolution of the mammalian limb: adaptive diversification of
nails, hooves, and claws. Evol Dev. 2001 Sep-Oct;3(5):355-63. Review.
Sharpe, PT. Fish scale development: Hair today, teeth and scales yesterday? Curr Biol. 2001
Sep 18;11(18):R751-2. Review.
Jeffrey WR. Cavefish as a model system in evolutionary developmental biology. Dev Biol. 2001
Mar 1;231(1):1-12. Review.
Tautz, D. Segmentation. Developmental Cell. (2004) Sept; 7(3): 301-12.
5/05/05
Take home Exam due (date may change)
6