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Contact inhibition/collapse and pathfinding of neural crest cells in the zebrafish trunk
1ICRF Developmental Biology Unit, Department of Zoology, Oxford, UK.
Abstract:
Neural crest cells in the trunk of vertebrate embryos have a choice of pathways after emigrating from the neural tube: they can migrate in either the medial pathway between somites and neural tube, or the lateral pathway between somites and epidermis. In zebrafish embryos, the first cells to migrate all choose the medial pathway. High resolution imaging of cells in living embryos suggests that neural crest cells do so because of repulsion by somites: cells take the medial pathway because the lateral somite surface triggers a paralysis and retraction of protrusions (contact inhibition or collapse) when the medial surface does not. Partial deletion of somites, using the spadetail mutation allows precocious entry into the lateral pathway, but only where somites are absent, supporting the notion that an inhibitory cue on somites delays entry. Growth cones of Rohon-Beard cells enter the lateral pathway before neural crest cells, demonstrating that there is no absolute barrier to migration. These data, in addition to providing a detailed picture of neural crest cells migrating in vivo, suggest that neural crest cells, like neuronal growth cones, are guided by a specific cue that triggers 'collapse' of active protrusions.
Insights
Neural crest cells in zebrafish embryos avoid the lateral pathway due to somite repulsion. This repulsion, mediated by contact inhibition, guides their migration along the medial pathway.
Area of Science:
- Developmental biology
- Cell migration
- Embryogenesis
Background:
- Neural crest cells (NCCs) are multipotent cells originating from the neural tube during vertebrate development.
- NCCs migrate extensively to form diverse cell types, including neurons and glia.
- The migratory pathways of NCCs are crucial for proper embryonic development.
Purpose of the Study:
- To investigate the guidance mechanisms of neural crest cell migration in zebrafish embryos.
- To determine the role of somites in directing NCCs towards the medial pathway.
- To elucidate the cellular basis for pathway choice in migrating NCCs.
Main Methods:
- High-resolution live imaging of zebrafish embryos.
- Analysis of NCC migration in wild-type and spadetail mutant zebrafish.
- Observation of Rohon-Beard cell growth cone migration.
Main Results:
- Zebrafish NCCs initially migrate exclusively through the medial pathway.
- Somites repel NCCs via contact inhibition, causing retraction of cellular protrusions.
- The spadetail mutation, causing partial somite deletion, allows premature lateral pathway entry where somites are absent.
- Rohon-Beard cell growth cones can access the lateral pathway, indicating no absolute barrier.
Conclusions:
- Somites provide a repulsive cue that directs neural crest cell migration to the medial pathway.
- Neural crest cell migration is guided by a specific inhibitory cue on somites, triggering protrusion collapse.
- This mechanism is analogous to guidance cues used by neuronal growth cones.