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Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance toward or away from the midline
M Seeger1, G Tear, D Ferres-Marco
1Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Abstract:
We performed a large-scale screen for mutations that affect the development of CNS axon pathways in the Drosophila embryo. We screened embryos from over 13,500 balanced lines and saved over 250 mutant lines whose phenotypes suggest possible defects in growth cone guidance. Here we focus on two new genes: commissureless (comm) and roundabout (robo). Mutations in comm lead to an absence of nearly all CNS axon commissures, such that growth cones that normally project across the midline instead now extend only on their own side. Mutations in robo lead to the opposite misrouting, such that some growth cones that normally extend only on their own side instead now project across the midline. The phenotypes of these two genes suggest that they may encode components of attractive and repulsive signaling systems at the midline that either guide growth cones across the midline or keep them on their own side.
Insights
Researchers screened over 13,500 Drosophila lines to find mutations affecting CNS axon guidance. Two genes, commissureless (comm) and roundabout (robo), were identified, revealing key mechanisms in growth cone pathfinding.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Central Nervous System (CNS) axon pathway development is crucial for organismal function.
- Growth cone guidance relies on complex signaling pathways at the embryonic midline.
Purpose of the Study:
- To identify novel genes regulating CNS axon pathway formation in Drosophila.
- To characterize the roles of commissureless (comm) and roundabout (robo) in growth cone guidance.
Main Methods:
- Large-scale genetic screen of over 13,500 balanced Drosophila lines.
- Phenotypic analysis of mutant embryos exhibiting defects in CNS axon commissures.
- Focus on mutations affecting growth cone guidance at the embryonic midline.
Main Results:
- Identified over 250 mutant lines with potential growth cone guidance defects.
- comm mutations resulted in the absence of CNS axon commissures.
- robo mutations caused misrouting of growth cones across the midline.
Conclusions:
- comm and robo genes are essential for proper CNS axon pathway development.
- These genes likely encode components of attractive and repulsive signaling systems at the midline.
- Findings provide insights into the molecular mechanisms of growth cone pathfinding.