Transient cell–cell interactions involving presynaptic neurons and cells that are extrinsic to the neural circuit have important roles in the assembly of the nervous system. In contrast to classically described environmental axon guidance cues, which attract or repel axons over long distances, these cell–cell interactions transiently mark a specific spatial coordinate and delineate choice points for axon growth or synaptogenesis.
These cell–cell interactions have diverse roles in patterning neuronal connectivity, including roles as intermediate targets in axon guidance, scaffolds for axonal growth, transient synaptic targets and guideposts for synapse target selection. Examples of these cell–cell interactions are found in many different organisms and diverse cellular contexts.
Many of the cells involved in transient cell–cell interactions have multiple roles in the development of the nervous system, including specification of neural precursors, neuronal migration and axon arborization.
The molecular mechanisms that underlie these transient cell–cell interactions include secretion of short-range attractive and repulsive cues, expression of cell surface adhesion molecules and secretion of long-range signals that pattern synaptic connectivity.
The wiring of the nervous system requires a complex orchestration of developmental events. Emerging evidence suggests that transient cell–cell interactions often serve as positional cues for axon guidance and synaptogenesis during the assembly of neural circuits. In contrast to the relatively stable cellular interactions between synaptic partners in mature circuits, these transient interactions involve cells that are not destined to be pre- or postsynaptic cells. Here we review the roles of these transient cell–cell interactions in a variety of developmental contexts and describe the mechanisms through which they organize neural connections.
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We thank members of K.S.'s laboratory for helpful discussions, M. Margeta for reading of the manuscript and the reviewers for their helpful suggestions. We apologize to authors whose work we were unable to include owing to space constraints.
- En passant synapses
Synapses formed along the shaft of the axon, in contrast to terminal synapses, which are formed only at the end of the axon.
- Pioneer axon
An axon that develops early in a fascicle and acts as a scaffold for later-developing neurons to grow on.
- Floor plate
Specialized neural epithelial cells found at the ventral midline of the spinal cord that secrete various factors involved in organizing the nervous system.
Secreted proteins similar to laminin that were first discovered through their involvement in axon guidance.
Axon guidance factors that were first discovered through their roles as chemorepellents.
- Optic chiasm
The anatomical landmark where retinal ganglion cell axons from both eyes converge and cross.
- Radial glia
Cells with astrocytic characteristics and processes that span the region from the lumen of the ventricle to the pial surface. They have multiple roles during neural development.
- Mitral cell
The main efferent output of the olfactory bulb.
- Bergmann glial cell
An astrocyte that extends long radial fibres throughout the entire cerebellum.
- Entorhinal cortex
The brain region that provides the main input to the hippocampus.
A secreted glycoprotein that is implicated in neuronal migration and other signalling pathways.
- Cajal–Retzius cell
One of the earliest-born classes of neurons. They are located along the surface of the entire cortex during most of cortical development.
- Lateral geniculate nucleus
The area of the thalamus that receives projections from the retina and sends projections to the visual cortex.
A transient cell layer located below the cortical plate early in development that is important for establishing thalamocortical projections.
A family of well-conserved secreted molecules that have multiple roles in cell–cell interactions.
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Chao, D., Ma, L. & Shen, K. Transient cell–cell interactions in neural circuit formation. Nat Rev Neurosci 10, 262–271 (2009). https://doi.org/10.1038/nrn2594
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