Advertisement
GET OUR E-ALERTS

Searching for Genes Underlying Behavior: Lessons from Circadian Rhythms

Joseph S. Takahashi, Kazuhiro Shimomura, and Vivek Kumar
Science • 7 Nov 2008 • Vol 322, Issue 5903 • pp. 909-912 • DOI: 10.1126/science.1158822
get access

Abstract

The success of forward genetic (from phenotype to gene) approaches to uncover genes that drive the molecular mechanism of circadian clocks and control circadian behavior has been unprecedented. Links among genes, cells, neural circuits, and circadian behavior have been uncovered in the Drosophila and mammalian systems, demonstrating the feasibility of finding single genes that have major effects on behavior. Why was this approach so successful in the elucidation of circadian rhythms? This article explores the answers to this question and describes how the methods used successfully for identifying the molecular basis of circadian rhythms can be applied to other behaviors such as anxiety, addiction, and learning and memory.
Get full access to this article

View all available purchase options and get full access to this article.

Get Access
Already a Subscriber?

Supplementary Material

File (takahashi.som.pdf)
Download

References and Notes

1
S. Benzer, Sci. Am.229, 24 (1973).
2
J. S. Takahashi, J. Biol. Rhythms19, 339 (2004).
3
R. J. Konopka, S. Benzer, Proc. Natl. Acad. Sci. U.S.A.68, 2112 (1971).
4
J. S. Takahashi, L. H. Pinto, M. H. Vitaterna, Science264, 1724 (1994).
5
D. Bell-Pedersenet al., Nat. Rev. Genet.6, 544 (2005).
6
J. S. Takahashi, H. K. Hong, C. H. Ko, E. L. McDearmon, Nat. Rev. Genet.9, 764 (2008).
7
D. R. Weaver, J. Biol. Rhythms13, 100 (1998).
8
D. P. Kinget al., Cell89, 641 (1997).
9
Z. S. Sunet al., Cell90, 1003 (1997).
10
H. Teiet al., Nature389, 512 (1997).
11
E. Nagoshiet al., Cell119, 693 (2004).
12
D. K. Welsh, S. H. Yoo, A. C. Liu, J. S. Takahashi, S. A. Kay, Curr. Biol.14, 2289 (2004).
13
S. H. Yooet al., Proc. Natl. Acad. Sci. U.S.A.101, 5339 (2004).
14
S. M. Siepka, J. S. Takahashi, Methods Enzymol.393, 230 (2005).
15
C. S. Pittendrigh, S. Daan, J. Comp. Physiol. A106, 223 (1976).
16
M. H. Vitaternaet al., Science264, 719 (1994).
17
K. T. Moortgat, T. H. Bullock, T. J. Sejnowski, J. Neurophysiol.83, 971 (2000).
18
M. H. Vitaterna, L. H. Pinto, J. S. Takahashi, Trends Neurosci.29, 233 (2006).
19
D. M. Bannerman, M. A. Good, S. P. Butcher, M. Ramsay, R. G. Morris, Nature378, 182 (1995).
20
M. Thomsen, S. B. Caine, Behav. Genet.37, 101 (2007).
21
E. A. Phelps, J. E. LeDoux, Neuron48, 175 (2005).
22
E. R. Kandel, Science294, 1030 (2001).
23
R. L. Davis, Physiol. Rev.76, 299 (1996).
24
P. L. Lowreyet al., Science288, 483 (2000).
25
J. P. DeBruyne, D. R. Weaver, S. M. Reppert, Nat. Neurosci.10, 543 (2007).
26
Q. J. Menget al., Neuron58, 78 (2008).
27
D. P. Kinget al., Genetics146, 1049 (1997).
28
The International Mouse Knockout Consortium, Cell128, 9 (2007).
29
Y. Gondo, Nat. Rev. Genet.9, 803 (2008).
30
A. Acevedo-Arozena et al., Annu. Rev. Genomics Hum. Genet.9, 49 (2008).
31
B. T. Kile, D. J. Hilton, Nat. Rev. Genet.6, 557 (2005).
32
S. M. Siepkaet al., Cell129, 1011 (2007).
33
A. Matyniaet al., PLoS One3, e2121 (2008).
34
J. Flint, W. Valdar, S. Shifman, R. Mott, Nat. Rev. Genet.6, 271 (2005).
35
L. L. Peterset al., Nat. Rev. Genet.8, 58 (2007).
36
W. F. Dietrichet al., Cell75, 631 (1993).
37
K. E. Strunk, V. Amann, D. W. Threadgill, Genetics167, 1821 (2004).
38
K. Shimomuraet al., Genome Res.11, 959 (2001).
39
J. H. Nadeau, W. N. Frankel, Nat. Genet.25, 381 (2000).
40
K. A. Frazeret al., Nature448, 1050 (2007).
41
D. R. Beier, Mamm. Genome11, 594 (2000).
42
E. R. Mardis, Annu. Rev. Genomics Hum. Genet.9, 387 (2008).
43
T. J. Albertet al., Nat. Methods4, 903 (2007).
44
E. Hodgeset al., Nat. Genet.39, 1522 (2007).
45
Supported by NIH grants U01 MH61915, R01 MH078024, and P50 MH074924 (Silvio O. Conte Center) to J.S.T., Takeda Research grant 07-030R to K.S., and NIH National Research Service Award F32 DA024556 to V.K. J.S.T. is an Investigator in the Howard Hughes Medical Institute.

Information & Authors

Information

Published In

Science
Volume 322 | Issue 5903
7 November 2008

Copyright

American Association for the Advancement of Science.

Submission history

Published in print: 7 November 2008

Permissions

Request permissions for this article.

Authors

Affiliations

Joseph S. Takahashi*
Howard Hughes Medical Institute, Northwestern University, Evanston, IL 60208, USA.
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA.
Center for Functional Genomics, Northwestern University, Evanston, IL 60208, USA.
View all articles by this author
Kazuhiro Shimomura
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA.
Center for Functional Genomics, Northwestern University, Evanston, IL 60208, USA.
View all articles by this author
Vivek Kumar
Howard Hughes Medical Institute, Northwestern University, Evanston, IL 60208, USA.
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA.
Center for Functional Genomics, Northwestern University, Evanston, IL 60208, USA.
View all articles by this author

Notes

* To whom correspondence should be addressed. E-mail: [email protected]

Metrics & Citations

Metrics

Article Usage
Altmetrics

Citations

Export citation

Select the format you want to export the citation of this publication.

Cited by
    • Sam-Moon Kim,
    • Chelsea A. Vadnie,
    • Vivek M. Philip,
    • Leona H. Gagnon,
    • Kodavali V. Chowdari,
    • Elissa J. Chesler,
    • Colleen A. McClung,
    • Ryan W. Logan,
    High-throughput measurement of fibroblast rhythms reveals genetic heritability of circadian phenotypes in diversity outbred mice and their founder strains, Scientific Reports, 11, 1, (2021).https://doi.org/10.1038/s41598-021-82069-8
    Crossref
    • Joseph S. Takahashi,
    The 50th anniversary of the Konopka and Benzer 1971 paper in PNAS: “Clock Mutants of Drosophila melanogaster ” , Proceedings of the National Academy of Sciences, 118, 39, (e2110171118), (2021).https://doi.org/10.1073/pnas.2110171118
    Crossref
    • Christopher S. Colwell,
    Defining circadian disruption in neurodegenerative disorders, Journal of Clinical Investigation, 131, 19, (2021).https://doi.org/10.1172/JCI148288
    Crossref
    • Dapeng Ju,
    • Wei Zhang,
    • Jiawei Yan,
    • Haijiao Zhao,
    • Wei Li,
    • Jiawen Wang,
    • Meimei Liao,
    • Zhancong Xu,
    • Zhiqiang Wang,
    • Guanshen Zhou,
    • Long Mei,
    • Nannan Hou,
    • Shuhua Ying,
    • Tao Cai,
    • She Chen,
    • Xiaowen Xie,
    • Luhua Lai,
    • Chao Tang,
    • Noheon Park,
    • Joseph S. Takahashi,
    • Niu Huang,
    • Xiangbing Qi,
    • Eric Erquan Zhang,
    Chemical perturbations reveal that RUVBL2 regulates the circadian phase in mammals, Science Translational Medicine, 12, 542, (2021)./doi/10.1126/scitranslmed.aba0769
    Abstract
    • Qingqing Lu,
    • Jin Young Kim,
    Mammalian circadian networks mediated by the suprachiasmatic nucleus, The FEBS Journal, (2021).https://doi.org/10.1111/febs.16233
    Crossref
    • Xiaoyue Pan,
    • Samantha Mota,
    • Boyang Zhang,
    Circadian Clock Regulation on Lipid Metabolism and Metabolic Diseases, Lipid Transfer in Lipoprotein Metabolism and Cardiovascular Disease, (53-66), (2020).https://doi.org/10.1007/978-981-15-6082-8_5
    Crossref
    • Agorastos Agorastos,
    • Miranda Olff,
    Traumatic stress and the circadian system: neurobiology, timing and treatment of posttraumatic chronodisruption, European Journal of Psychotraumatology, 11, 1, (1833644), (2020).https://doi.org/10.1080/20008198.2020.1833644
    Crossref
    • Evan S. Littleton,
    • Madison L. Childress,
    • Michaela L. Gosting,
    • Ayana N. Jackson,
    • Shihoko Kojima,
    Genome-wide correlation analysis to identify amplitude regulators of circadian transcriptome output, Scientific Reports, 10, 1, (2020).https://doi.org/10.1038/s41598-020-78851-9
    Crossref
    • Huei Bin Wang,
    • Yu Tahara,
    • Shu Hon Christopher Luk,
    • Yoon-Sik Kim,
    • Olivia N. Hitchcock,
    • Zoe A. MacDowell Kaswan,
    • Yang In Kim,
    • Gene D. Block,
    • Cristina A. Ghiani,
    • Dawn H. Loh,
    • Christopher S. Colwell,
    Melatonin treatment of repetitive behavioral deficits in the Cntnap2 mouse model of autism spectrum disorder, Neurobiology of Disease, 145, (105064), (2020).https://doi.org/10.1016/j.nbd.2020.105064
    Crossref
    • Agorastos Agorastos,
    • Nicolas C. Nicolaides,
    • Vasilios P. Bozikas,
    • George P. Chrousos,
    • Panagiota Pervanidou,
    Multilevel Interactions of Stress and Circadian System: Implications for Traumatic Stress, Frontiers in Psychiatry, 10, (2020).https://doi.org/10.3389/fpsyt.2019.01003
    Crossref
  11. See more

View Options

Get Access

Log in to view the full text

AAAS ID LOGIN

AAAS login provides access to Science for AAAS Members, and access to other journals in the Science family to users who have purchased individual subscriptions.

Log in via OpenAthens.
via OpenAthens
Log in via Shibboleth.
via Shibboleth
More options

Purchase digital access to this article

Download and print this article for your personal scholarly, research, and educational use.

Purchase this issue in print

Buy a single issue of Science for just $15 USD.

View options

PDF format

Download this article as a PDF file

Download PDF

Media

Figures

Multimedia

Tables

Share

Share

Share article link

Share on social media

Current Issue

Go to Science
Table of Contents

LATEST NEWS