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Published on: March 8, 2010
The E3 ubiquitin ligase Mycbp2 genetically interacts with Robo2 to modulate axon guidance in the mouse olfactory
1Brain Growth and Regeneration Lab, School of Biomedical Sciences, University of Queensland, Brisbane, 4072, Australia.
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.
Insights
The E3 ubiquitin ligase Mycbp2 is crucial for guiding olfactory sensory neuron axons in mice. Loss of Mycbp2 function disrupts axon pathfinding, revealing its cooperation with Robo2 in neural development.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Mycbp2 (Mothers against decapentaplegic homolog 2) is an E3 ubiquitin ligase with conserved roles in axon guidance and synaptogenesis across species.
- The precise molecular and cellular mechanisms underlying Mycbp2-mediated axon guidance are not well understood.
Purpose of the Study:
- To investigate the role of Mycbp2 in the topographic projection of olfactory sensory neurons to the olfactory bulb in mice.
- To elucidate the genetic interactions between Mycbp2 and Robo2 in mammalian axon guidance.
Main Methods:
- Analysis of olfactory sensory neuron projection patterns in mice with loss-of-function mutations in Mycbp2.
- Examination of double heterozygous mice (Mycbp2 and Robo2) to assess genetic cooperation.
- Investigation of olfactory sensory neuron patterning and Robo2 expression in the nasal cavity.
Main Results:
- Loss of Mycbp2 function in mice leads to aberrant topography of olfactory sensory neuron projections to the olfactory bulb.
- These defects resemble those observed in Robo2-deficient mice, suggesting a functional link.
- Double heterozygous mice for Mycbp2 and Robo2 exhibit severe olfactory system defects, indicating genetic cooperation.
- Aberrant patterning and reduced Robo2 expression in dorsal nasal cavity olfactory sensory neurons correlate with ventral olfactory bulb projection defects.
Conclusions:
- Mycbp2 and Robo2 function cooperatively within a genetic network critical for olfactory axon guidance in mice.
- This study provides the first evidence linking an E3 ubiquitin ligase to an axon guidance receptor in mammalian nervous system development.
- Mycbp2 influences olfactory sensory neuron patterning, impacting Robo2 expression and subsequent axon pathfinding.
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