The E3 ubiquitin ligase Mycbp2 genetically interacts with Robo2 to modulate axon guidance in the mouse olfactory system

James, G., Key, B. and Beverdam, A. (2014) The E3 ubiquitin ligase Mycbp2 genetically interacts with Robo2 to modulate axon guidance in the mouse olfactory system. Brain Structure and Function, 219 3: 861-874. doi:10.1007/s00429-013-0540-8

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads

Author James, G.
Key, B.
Beverdam, A.
Title The E3 ubiquitin ligase Mycbp2 genetically interacts with Robo2 to modulate axon guidance in the mouse olfactory system
Formatted title
The E3 ubiquitin ligase Mycbp2 genetically interacts with Robo2 to modulate axon guidance in the mouse olfactory system
Journal name Brain Structure and Function   Check publisher's open access policy
ISSN 1863-2653
1863-2661
Publication date 2014-05-01
Year available 2013
Sub-type Article (original research)
DOI 10.1007/s00429-013-0540-8
Open Access Status
Volume 219
Issue 3
Start page 861
End page 874
Total pages 14
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Abstract The E3 ubiquitin ligase Mycbp2 and it homologues play an important role in axon guidance and synaptogenesis in Drosophila, Caenorhabditis elegans, zebrafish and mouse. Despite this conserved function, the molecular and cellular basis of Mycbp2-dependent axon guidance remains largely unclear. We have examined here the effect of the loss-of-MYCBP2 function on the topography of the olfactory sensory neuron projection from the nasal cavity to the olfactory bulb in mice. A subpopulation of olfactory sensory axons failed to project to the dorsal surface of the olfactory bulb causing abnormal topography in this neural pathway. These defects were similar to the olfactory bulb phenotype in loss-of-ROBO2 function mice. While mice heterozygous for either Mycbp2 or Robo2 were normal, mice double heterozygous for these two genes produced severe defects in the olfactory system. Therefore, Mycbp2 and Robo2 were found to cooperate within a genetic network that has profound effects on axon guidance. The Mycbp2 phenotype could be partly explained by aberrant patterning of olfactory sensory neurons residing in the dorsal compartment of the nasal cavity. Some of these neurons fail to appropriately express Robo2 which is consistent with their aberrant projection to the ventral olfactory bulb. These results provide the first evidence linking an ubiquitin ligase to an axon guidance receptor during pathfinding in the developing mammalian nervous system.
Formatted abstract
The E3 ubiquitin ligase Mycbp2 and it homologues play an important role in axon guidance and synaptogenesis in Drosophila, Caenorhabditis elegans, zebrafish and mouse. Despite this conserved function, the molecular and cellular basis of Mycbp2-dependent axon guidance remains largely unclear. We have examined here the effect of the loss-of-MYCBP2 function on the topography of the olfactory sensory neuron projection from the nasal cavity to the olfactory bulb in mice. A subpopulation of olfactory sensory axons failed to project to the dorsal surface of the olfactory bulb causing abnormal topography in this neural pathway. These defects were similar to the olfactory bulb phenotype in loss-of-ROBO2 function mice. While mice heterozygous for either Mycbp2 or Robo2 were normal, mice double heterozygous for these two genes produced severe defects in the olfactory system. Therefore, Mycbp2 and Robo2 were found to cooperate within a genetic network that has profound effects on axon guidance. The Mycbp2 phenotype could be partly explained by aberrant patterning of olfactory sensory neurons residing in the dorsal compartment of the nasal cavity. Some of these neurons fail to appropriately express Robo2 which is consistent with their aberrant projection to the ventral olfactory bulb. These results provide the first evidence linking an ubiquitin ligase to an axon guidance receptor during pathfinding in the developing mammalian nervous system.
Keyword Mycbp2
Robo
Olfactory
Axon guidance
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 24 March 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 3 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 4 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sat, 01 Feb 2014, 02:38:41 EST by Professor Brian Key on behalf of School of Biomedical Sciences