Matthew Wood, Department of Human Anatomy and Genetics
The material covered in this lecture and the further reading should enable you to:
- Understand how RNA is transcribed and processed within neurons
- Understand methods for analyzing gene expression
- Understand how mRNA is translated and protein targeted within complex cells such as neurons
- Understand methods for determining mRNA / protein localization and function within the CNS
1. Differentiation arises as a result of differential gene expression during development
2. Proneural genes and the specification of neural cell types. Nature Reviews Neuroscience 3, 517-530 (2002) http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrn/journal/v3/n7/full/nrn874_fs.html
3. Kim, JH et al. (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature 418: 50-6 http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v418/n6893/full/nature00900_fs.html
4. Gene expression is regulated at multiple levels (transcription, splicing, mRNA transport, translation, post-translation)
5. Transcription is regulated by cis-acting sequences and trans-acting DNA-binding proteins
6. Splicing removes introns from pre-mRNA
7. There are multiple forms of RNA: rRNA, tRNA, mRNA, snRNA
8. siRNA: Gene silencing in mammals by small interfering RNAs. Nature Reviews Genetics 3, 737 -747 (2002) at http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrg/journal/v3/n10/abs/nrg908_fs.html&dynoptions=doi1035816080
9. Alternative splicing generates multiple transcripts by selective exon excision.
10. The splice of life: alternative splicing and neurological disease. Nature Reviews Neuroscience 2, 43-50 (2001) at http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrn/journal/v2/n1/full/nrn0101_043a_fs.html
11. Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability. Neuron 2000, 25:359-71
12. Northern blotting (mRNA hybridization) or in situ hybridization allow the monitoring of mRNA expression in cells and tissues
13. cDNA microarrays are used for monitoring the transcriptome (Nature Reviews Neuroscience 2001 2, 435-438 see at: http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrn/journal/v2/n6/full/nrn0601_435a_fs.html)
14. Localization and translation of mRNA in dendrites and axons. Nature Reviews Neuroscience 2, 889-898 (2001) at http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrn/journal/v2/n12/full/nrn1201-889a_fs.html
1. Proteins are produced by translation of mRNA
2. Immunocytochemistry and Western blotting make use of antibodies to monitor protein expression
3. The proteome is the collection of all proteins expressed in a cell or tissue
4. NB. Nature genome and proteome information at: http://www.nature.com/genomics/
1. Motor neuron degeneration e.g. neurofilament and SOD1 genes (see review at: http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrn/journal/v2/n11/full/nrn1101-806a_fs.html )
2. Myelin mutations e.g. PLP gene (The proteolipid protein gene and myelin disorders in man and animal models. Hum Mol Genet. 2000; 9: 987-92 see at: http://hmg.oupjournals.org/cgi/content/full/9/6/987 )
3. Trinucleotide repeat mutations e.g. Huntington’s disease (Fourteen and counting: unraveling trinucleotide repeat diseases Hum Mol Genet 2000; 9: 909-916 see at: http://hmg.oupjournals.org/cgi/content/full/9/6/909)
4. Transcriptional dysregulation in HD Trends in Neurosciences 2000, 23:387-392 (see at: http://reviews.bmn.com/browse/areas/record?uid=TINS.etd00449_01662236_v0023i09_00001609&rendertype=)
Nature focus on stem cells: http://www.nature.com/reviews/focusarticles/stem_cell/
Science special issue on stem cells: http://www.sciencemag.org/content/vol287/issue5457/index.shtml
Nature focus on neural development: http://www.nature.com/nrn/focus/neurodev/
Nature genome gateway: http://www.nature.com/genomics/index.html
Nature profiling microarrays: http://www.nature.com/genomics/post-genomics/microarrays.html
Nature proteomics in action: http://www.nature.com/genomics/post-genomics/action.html
Nature computational genomics: http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrg/journal/v2/n6/full/nrg0601_418a_fs.html
Nature genetics links: http://www.nature.com/nrg/info/info_links.html
Neurosciences on the internet: http://www.neuroguide.com/
National centre for biotechnology information: http://www.ncbi.nlm.nih.gov/
mjaw
30.x.2002
Contact: matthew.wood@anat.ox.ac.uk