Biol 376: Developmental Neurobiology

Professor Elena Casey

3 credits  W 2:15- 4:45 PM

Fall 2008

 

Course Description: This guided seminar course introduces upper level undergraduates to selected topics of the development of the nervous system of vertebrates and invertebrates. Students will read, present and discuss review articles and primary research literature investigating molecular, cellular, evolutionary and embryological aspects of neurodevelopment. Topics will include dorsal-ventral patterning, induction of the neural plate, neuronal differentiation, axon guidance, and synapse formation. Recent technological advances of each subject and the representation of these topics by the media to the lay public will be discussed.

 

Goals: The objective of this course is to introduce students to fundamental neurodevelopmental processes.  We will focus on milestones in neurodevelopment and the molecular, embryological, biochemical and cellular approaches that were used to reach these points. Rather than exploring a wide spectrum of systems and processes, this course is designed to examine selected topics in pattern formation and cell fate specification in considerable depth. While we will also examine some of the more controversial aspects of neurodevelopment and discuss the ethics of this research, this course emphasizes analysis of research articles.

 

At the completion of this course student will be able to:

  • Describe the importance of a multi-disciplinary approach to understanding the nervous system.
  • Describe how molecular, cellular, embryological and behavioral studies have contributed to our understanding of the nervous system.
  • Identify and explain why research questions rather than methods ideally drive advances in development.
  • Compare textbook, popular and peer-reviewed scholarly reports in neurodevelopment.
  • Understand various experimental techniques used in developmental neurobiology.
  • Discuss topics in developmental neurobiology formally and informally with scientists.
  • Identify appropriate applications of neurodevelopment knowledge in health, service, policy, education, or business, professions.
  • Devise neurodevelopment hypotheses in feasible and solvable ways. 
  • Create and communicate reasoned arguments about major issues related to the development of the nervous system.

 

Format:

Each class period, students will answer questions on review articles and lay news reports followed by a break, a student presentation of a research article using powerpoint and finally the last 30 minutes of each class will be a brief review of the following week’s topic. To ensure participation in the discussions of review articles, students 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. Also, students will turn in answers to a problem set on the research paper and the presenter may feel free to pose these questions to the class during his/her presentation.

 

The student presentation must be discussed on the Monday before class with Dr. Casey and the completed electronic version must be sent to her the night before.

 

Course Policies:

  • Attendance
    • You are required to attend class. If you have a legitimate reason to miss class you must discuss this with me prior to the class and provide written verification of your excuse (e.g. note from doctor, email from medical school for interview). If you miss class, be sure to turn in assignments on time and you will be given a zero for that day until you complete an extra homework assignment. It is your responsibility to get this assignment from me and to get any notes from students in the class.
  • Expectations—I expect you to:
    • Be on time to class
    • Do all of the assigned readings
    • Participate actively in discussions
    • Refer to the syllabus and blackboard continually
    • Turn off cell phone prior to the start of class
  • Honor code
    • All work done in connection with this class is bound by the Georgetown honor system. While you are encouraged to study together, all written work must be your own. As responsible scholars, I expect you to identify the source for any ideas that are not your own even if you do not quote the source directly. In fact in this class, direct quotes will not be accepted – you must show that you understand difficult scientific ideas by paraphrasing and describing the difficult scientific sentences and jargon. USE YOUR OWN WORDS!
  • Late or absent homework or exams
    • You will drop one letter grade for every day or part of day that fail to turn in homework.

 

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:

Optional textbook reading:

1.      Rao and Jacobson. Developmental Neurobiology 4th edition

2.      Reference text on reserve in Science Library:

      Gilbert, Scott F. Developmental Biology 6th, 7th or 8th edition

      The 6th ed is available at NCBI bookviewer:

      http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=dbio.TOC&depth=2

 

Grading:        

10%     in class participation (including answering provided questions)

            15%     powerpoint presentation

            25%     take home midterm   

            25%     written problem sets

25%     take home final                       

 

Assignments:

9/3       Introduction and Conserved pathways in dorsal-ventral patterning development

Background reading ( if you feel lost with the review):

Gilbert 8th edition pp 305-316

 

Review:

De Robertis, E. M. & Sasai, Y. A common plan for dorsoventral patterning in Bilateria. Nature 380, 37-40 (1996).           

Gee NATURE. Vol 445, 4 January 2007, News and views

 

Research Article:

Piccolo S, Sasai Y, Lu B, De Robertis EM. Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct binding of chordin to BMP-4. Cell. 1996 Aug 23;86(4):589-98.

 

 

9/10    Neurulation 

Review:

Copp AJ, Greene ND, Murdoch JN. The genetic basis of mammalian neurulation.

Nat Rev Genet. 2003 Oct;4(10):784-93. Review.

 

Research Articles:

Haigo SL, Hildebrand JD, Harland RM, Wallingford JB. Shroom induces apical constriction and is required for hingepoint formation during neural tube closure. Curr Biol. 2003 Dec 16;13(24):2125-37.

Kim TH, Goodman J, Anderson KV, Niswander L. Phactr4 regulates neural tube and optic fissure closure by controlling PP1-, Rb-, and E2F1-regulated cell-cycle progression.

Dev Cell. 2007 Jul;13(1):87-102.

 

 

9/17  A-P patterning – Caudal induction/transformation and Organizers The CNS is organized into an anterior forebrain and midbrain and posterior hindbrain anf spinal cord. How and when is this pattern established? Specific regions (organizers) in the brain such as the MHB(mid-hindbrain barrier) are important in generating regionalized patterns.

 

Background reading:

Gilbert  8th ed: 316-322 ( Ch 10 The regional specificity of induction)

Review:

Stern CD (2001). Initial patterning of the central nervous system: how many organizers? Nat. Rev. Neurosci. 2: 92 – 98.      

Raible F, Brand M. Divide et Impera--the midbrain-hindbrain boundary and its organizer.

Trends Neurosci. 2004 Dec;27(12):727-34.

 

Article:

Dupé V, Lumsden A. Hindbrain patterning involves graded responses to retinoic acid signalling.

Development. 2001 Jun;128(12):2199-208.

Skim  -  Abu-Abed S, Dollé P, Metzger D, Beckett B, Chambon P, Petkovich M. The retinoic acid-metabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posterior structures. Genes Dev. 2001 Jan 15;15(2):226-40.

Jászai J, Reifers F, Picker A, Langenberg T, Brand M. Isthmus-to-midbrain transformation in the absence of midbrain-hindbrain organizer activity. Development. 2003 Dec;130(26):6611-23.

 

9/24 D-V Patterning of the spinal cord

The spinal cord is organized such that there are dorsal sensory neurons and ventral motor neurons. How and when is this pattern established? The protein shh which is secreted from the floor plate and the notochord plays a key role.

 

Background reading:

Nature milestones handout 1 (morphogens)

Nature milestones handout 2  (shh)

Review:

Jessell TM. (2000). Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat. Rev. Genet. 1: 20 – 29. focus on pages 20-25 and only skim the rest.

 

We will discuss:

Floor plate inductions Debate:

Placzek M, Dodd J, Jessell TM. (2000). The case for floor plate induction by the notochord. Current Opinion In Neurobiology 10:15–22.
Le Dourain NM and Halpern ME. (2000). The origin and specification of the neural tube floor plate: insights from the chick and zebrafish. Current Opinion In Neurobiology 10:15–22.
Patten I and M Placzek (2002). Opponent acitivities of shh and BMP signaling during floor plate induction in vivo. Current Biology 12: 47 - 52.

 

10/1    Neural crest and cranial placodes

These cells are derivative of the ectoderm and form the PNS and the cranial skeleton (neural crest) and sensory organs (placodes).

Background reading:

Review:

Schlosser G. Do vertebrate neural crest and cranial placodes have a common evolutionary origin? Bioessays. 2008 Jul;30(7):659-72.

Janvier P. Evolutionary biology: born-again hagfishes. Nature. 2007 Apr 5;446(7136):622-3.

Bronner-Fraser M. Development. Making sense of the sensory lineage. Science. 2004 Feb 13;303(5660):966-8.

 

Research articles:

Bailey AP, Bhattacharyya S, Bronner-Fraser M, Streit A. Lens specification is the ground state of all sensory placodes, from which FGF promotes olfactory identity. Dev Cell. 2006 Oct;11(4):505-17.

Tobin JL, Di Franco M, Eichers E, May-Simera H, Garcia M, Yan J, Quinlan R, Justice MJ, Hennekam RC, Briscoe J, Tada M, Mayor R, Burns AJ, Lupski JR, Hammond P, Beales PL.

Inhibition of neural crest migration underlies craniofacial dysmorphology and Hirschsprung's disease in Bardet-Biedl syndrome. Proc Natl Acad Sci U S A. 2008 May 6;105(18):6714-9. Epub 2008 Apr 28.

 

10/8    Neurogenesis- proneural proteins

Ectodermal cells are first induced to become neural precursor cells. The Np cells proliferate and then undergo neurogenesis – the process of differentiation into specific neuronal subtypes.essential to this process is the expression of proneural proteins and the SoxC proteins. How is this transition from proliferating precursor to post-mitotic neuron regulated?

 

Background reading:

Baker NE. Atonal points the way- protein-protein interactions and developmental biology.

Dev Cell. 2004 Nov;7(5):632-4.

Lai HC, Johnson JE. Neurogenesis or neuronal specification: phosphorylation strikes again!

Neuron. 2008 Apr 10;58(1):3-5.

 

Review: Kiefer JC, Jarman A, Johnson J. Pro-neural factors and neurogenesis. Dev Dyn. 2005 Nov;234(3):808-13.

Gould E, Gross CG. Neurogenesis in adult mammals: some progress and problems.

J Neurosci. 2002 Feb 1;22(3):619-23.

 

Potential Research articles:

Bergsland M, Werme M, Malewicz M, Perlmann T, Muhr J. The establishment of neuronal properties is controlled by Sox4 and Sox11. Genes Dev. 2006 Dec 15;20(24):3475-86.

Akai et al. FGF-dependent Notch signaling maintains the spinal cord stem zone. Genes & Dev. 2005 19: 2877-2887;

Gowan K, Helms AW, Hunsaker TL, Collisson T, Ebert PJ, Odom R, Johnson JE. Crossinhibitory activities of Ngn1 and Math1 allow specification of distinct dorsal interneurons.

Neuron. 2001 Aug 2;31(2):219-32.

Petersen PH, Zou K, Hwang JK, Jan YN, Zhong W. Progenitor cell maintenance requires numb and numblike during mouse neurogenesis. Nature. 2002 Oct 31;419(6910):929-34.

 

10/15  Glia

Neural-derived Glia is composed of oligodendrocytes and astrocytes. Like neurons, these cells orginate from neural precursors and play a variety of important roles in formation of the PNS and CNS. What regulates their specification and their unique structure?

 

Background reading:

Reviews:

Freeman MR. Sculpting the nervous system: glial control of neuronal development.

Curr Opin Neurobiol. 2006 Feb;16(1):119-25.

Rowitch DH. Glial specification in the vertebrate neural tube. Nat Rev Neurosci. 2004 May;5(5):409-19.

 

Research Articles:

Nieto M, Schuurmans, O Brz, F Guillemot Neural bHLH genes control the neuronal versus glial fate decision in cortical progenitors. 2001 Neuron 29: 401 – 413.
Tanigaki K, F Nogaki, …, T Honjo Notch1, Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate. 2001 Neuron 29:45 – 55.

Miller, Gauthier (2007) Timing is everything: making neurons versus glia in the developing cortex. Neuron 54:357-369

 

Group 1

10/17 – RECEIVE MIDTERM

10/20- Turn in MIDTERM

 

10/22 Cerebral cortex- birth and migration

How is the multilayered cerebral cortex formed? What is the role of migration and how do neurons find their final destination?

Background reading:

Götz M, Huttner WB. The cell biology of neurogenesis. Nat Rev Mol Cell Biol. 2005 Oct;6(10):777-88

Campbell K. Cortical neuron specification: it has its time and place. Neuron. 2005 May 5;46(3):373-6.

Nadarajah, Parnavelas (2002) Modes of neuronal migration in the developing cerebral cortex. Nat Rev Neurosci 3:423-432

 

Research articles:

Anthony TE, Klein C, Fishell G, Heintz N. Radial glia serve as neuronal progenitors in all regions of the central nervous system. Neuron. 2004 Mar 25;41(6):881-90.

 

Group II

10/23 RECEIVE MIDTERM

10/27 TURN IN MIDTERM Midterm Due on 10/25

 

10/29 Axon Guidance Growing axons are alternately attracted towards and repelled from a series of intermediate targets, through the carefully coordinated expression of specific guidance receptors. What are these targets and how do control axon movement.

 

Reviews:

Chilton (2006) Molecular mechanisms of axon guidance. Developmental Biology 292:13-24

Lopez-Bendito et al. (2007) Robo1 and Robo2 cooperate to control the guidance of major axonal tracts in the mammalian forebrain. J Neurosci 27:3395-3407

 

11/5    Synaptogenesis

Reviews:

Nam, Chen (2005) Postsynaptic assembly induced by neurexin-neuroligin interaction and neurotransmitter. Proc Natl Acad Sci USA 102:6137-6142

 

11/12 Regeneration and repair

Reviews:

Hoopfer et al. (2006) Wlds protection distinguishes axon degeneration following injury from naturally occurring developmental pruning. Neuron 50:883-95

Ullian et al. (2004) Role for glia in synaptogenesis. Glia 47:209-216

Yiu, He (2006) Glial inhibition of CNS axon regeneration. Nat Rev Neurosci 7:617-627

 

11/19 Disease

Reviews:

Courchesne E, Pierce K, Schumann CM, Redcay E, Buckwalter JA, Kennedy DP, Morgan J. Mapping early brain development in autism. Neuron. 2007 Oct 25;56(2):399-413.

Space invaders Nature Reviews Neuroscience 10 April 2008

 

Research Articles:
Oberheim, N. A. et al. Loss of astrocytic domain organization in the epileptic brain. J. Neurosci. (2008) 28, 3264–3276

 

 

11/26 Thanksgiving WEEK NO Class

 

 

12/3 Neural stem cells

Review:

Ramalho-Santos M, Yoon S, …, Melton D. (2002). “Stemness”. 298: 597-600.

Cremisi et al. (2003) Cell cycle and cell fate interactions in neural development. Curr Opin Neurobiol 13:26-3

 

Research Articles:

Kriegstein, Noctor, Martinez-Cerdeno (2006) Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion. Nat. Rev. Neurosci. 7:883-890

Song H, CF Stevens, and FH Gage. (2002) Astroglia induce neurogenesis from adult neural stem cells. Nature 417: 39 – 44.

 

FINAL received 12/6- DUE 12/17