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Redundancy and compensation in axon guidance: genetic analysis of the Drosophila Ptp10D/Ptp4E receptor tyrosine phosphatase subfamily

Jeon, Mili and Nguyen, Huong and Bahri, Sami and Zinn, Kai (2008) Redundancy and compensation in axon guidance: genetic analysis of the Drosophila Ptp10D/Ptp4E receptor tyrosine phosphatase subfamily. Neural Development, 3 (3). ISSN 1749-8104. PMCID PMC2270841. https://resolver.caltech.edu/CaltechAUTHORS:JEOnd08

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Abstract

Background: Drosophila has six receptor protein tyrosine phosphatases (RPTPs), five of which are expressed primarily in neurons. Mutations in all five affect axon guidance, either alone or in combination. Highly penetrant CNS and motor axon guidance alterations are usually observed only when specific combinations of two or more RPTPs are removed. Here, we examine the sixth RPTP, Ptp4E, which is broadly expressed. Results: Ptp4E and Ptp10D are closely related Type III RPTPs. Non-drosophilid insect species have only one Type III RPTP, which is closest to Ptp10D. We found that Ptp4E mutants are viable and fertile. We then examined Ptp4E Ptp10D double mutants. These die before the larval stage, and have a mild CNS phenotype in which the outer longitudinal 1D4 bundle is frayed. Ptp10D Ptp69D double mutants have a strong CNS phenotype in which 1D4 axons abnormally cross the midline and the outer and middle longitudinal bundles are fused to the inner bundle. To examine if Ptp4E also exhibits synthetic phenotypes in combination with Ptp69D, we made Ptp4E Ptp69D double mutants and Ptp4E Ptp10D Ptp69D triple mutants. No phenotype was observed in the double mutant. The triple mutant phenotype differs from the Ptp10D Ptp69D phenotype in two ways. First, the longitudinal tracts appear more normal than in the double mutant; two or three bundles are observed, although they are disorganized and fused. Second, axons labelled by the SemaIIB-tMyc marker often cross in the wrong commissure. We also examined motor axon guidance, and found that no phenotypes are observed in any Ptp4E double mutant combination. However, triple mutants in which Ptp4E Ptp10D was combined with Ptp69D or Ptp52F exhibited stronger phenotypes than the corresponding Ptp10D double mutants. Conclusions: Type III RPTPs are required for viability in Drosophila, since Ptp4E Ptp10D double mutants die before the larval stage. Unlike Ptp10D, Ptp4E appears to be a relatively minor player in the control of axon guidance. Strong phenotypes are only observed in triple mutants in which both Type III RPTPs are eliminated together with Ptp69D or Ptp52F. Our results allow us to construct a complete genetic interaction matrix for all six of the RPTPs.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1186/1749-8104-3-3DOIArticle
http://neuraldevelopment.biomedcentral.com/articles/10.1186/1749-8104-3-3PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270841/PubMed CentralArticle
ORCID:
AuthorORCID
Zinn, Kai0000-0002-6706-5605
Additional Information:© 2008 Jeon et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Submission date 22 October 2007. Acceptance date 31 January 2008. Publication date 31 January 2008. We thank the Caltech Protein Expression Facility and Caltech Monoclonal Facility for generation of proteins and antibodies. We also want to thank the Zinn group members for helpful discussions. This work was supported by an NIH RO1 grant, NS28182, to KZ. Competing interests: The authors declare that they have no competing interests. Authors' contributions: MJ carried out the genetic and molecular studies, and wrote the paper together with KZ. HN participated in the genetic studies and sequence alignment/evolutionary studies. SB isolated the Ptp4E mutant allele and isolated the full-length cDNA. KZ participated in the genetic studies and wrote the paper together with MJ. All authors read and approved the final manuscript.
Issue or Number:3
PubMed Central ID:PMC2270841
Record Number:CaltechAUTHORS:JEOnd08
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:JEOnd08
Usage Policy:© 2008 Jeon et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ID Code:9666
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:26 Feb 2008
Last Modified:12 Dec 2019 17:07

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