- THIS ARTICLE
- Full Text
- Full Text (PDF)
- Data Supplement
-
All Versions of this Article:
genetics.107.072819v1
176/4/2247 most recent - Alert me when this article is cited
- Alert me if a correction is posted
- SERVICES
- Email this article to a friend
- Similar articles in this journal
- Similar articles in PubMed
- Alert me to new issues of the journal
- Download to citation manager
- Reprints & Permissions
- CITING ARTICLES
- Citing Articles via HighWire
- Citing Articles via Google Scholar
- GOOGLE SCHOLAR
- Articles by Mindorff, E. N.
- Articles by van Meyel, D. J.
- Search for Related Content
- PUBMED
- PubMed Citation
- Articles by Mindorff, E. N.
- Articles by van Meyel, D. J.
Originally published as Genetics Published Articles Ahead of Print on July 1, 2007.
Genetics, Vol. 176, 2247-2263, August 2007, Copyright © 2007
doi:10.1534/genetics.107.072819
A Gain-of-Function Screen for Genes That Influence Axon Guidance Identifies the NF-
B Protein Dorsal and Reveals a Requirement for the Kinase Pelle in Drosophila Photoreceptor Axon Targeting
Elizabeth N. Mindorff*,
David D. O'Keefe
,1,
Alain Labbé
,
Jennie Ping Yang,
Yimiao Ou*,
Shingo Yoshikawa and
Donald J. van Meyel,
,**,2
* Graduate Program in Neurological Sciences, Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3G 1A4, Canada, The Salk Institute for Biological Studies, La Jolla, California 92037 and ** McGill University Health Centre Research Institute, Montreal, Quebec H3G 1A4, Canada
2 Corresponding author: McGill University Centre for Research in Neuroscience, Montreal General Hospital, L7-221 1650 Cedar Ave., Montreal, QC H3G 1A4, Canada.
E-mail: don.vanmeyel{at}mcgill.ca
To identify novel regulators of nervous system development, we used the GAL4-UAS misexpression system in Drosophila to screen for genes that influence axon guidance in developing embryos. We mobilized the Gene Search (GS) P element and identified 42 lines with insertions in unique loci, including leak/roundabout2, which encodes an axon guidance receptor and confirms the utility of our screen. The genes we identified encode proteins of diverse classes, some acting near the cell surface and others in the cytoplasm or nucleus. We found that one GS line drove misexpression of the NF-
B transcription factor Dorsal, causing motor axons to bypass their correct termination sites. In the developing visual system, Dorsal misexpression also caused photoreceptor axons to reach incorrect positions within the optic lobe. This mistargeting occurred without observable changes of cell fate and correlated with localization of ectopic Dorsal in distal axons. We found that Dorsal and its inhibitor Cactus are expressed in photoreceptors, though neither was required for axon targeting. However, mutation analyses of genes known to act upstream of Dorsal revealed a requirement for the interleukin receptor-associated kinase family kinase Pelle for layer-specific targeting of photoreceptor axons, validating our screen as a means to identify new molecular determinants of nervous system development in vivo.
This article has been cited by other articles:
 |
|
 |
|
  M. C. Boersma and M. K. Meffert Novel Roles for the NF-{kappa}B Signaling Pathway in Regulating Neuronal Function Sci. Signal., February 12, 2008; 1(6): pe7 - pe7. [Abstract] [Full Text] [PDF]
|
|