Abstract
Development of complex neural circuits like the peripheral somatosensory system requires intricate mechanisms to ensure axons make proper connections. While much is known about ligand-receptor pairs required for dorsal root ganglion (DRG) axon guidance, very little is known about the cytoplasmic effectors that mediate cellular responses triggered by these guidance cues. Here we show that members of the Cas family of cytoplasmic signaling adaptors are highly phosphorylated in central projections of the DRG as they enter the spinal cord. Furthermore, we provide genetic evidence that Cas proteins regulate fasciculation of DRG sensory projections. These data establish an evolutionarily conserved requirement for Cas adaptor proteins during peripheral nervous system axon pathfinding. They also provide insight into the interplay between axonal fasciculation and adhesion to the substrate.
Highlights
Precise assembly of the peripheral somatosensory system involves migration of neural crest cells (NCCs) to coalesce into sensory ganglia and subsequent guidance of axonal projections from these newly formed ganglia
Cas genes are broadly expressed in the dorsal root ganglion (DRG), but display specific regional expression in spinal cord (SC) at embryonic day (e)10.5 and e11.5 (Fig. 1a–f; Supplementary Fig. S1a–c). p130Cas is mainly expressed in the mantle zone, with high levels of expression in the dorsal SC and ventral root (Fig. 1d)
Sin/EFS is expressed around the ventricular zone of the SC, and subsets of DRG neurons (Fig. 1f). p130Cas and Sin continue to be expressed in the DRG at e12.5 and e14.5 (Fig. 1g,i,j,l)
Summary
Precise assembly of the peripheral somatosensory system involves migration of neural crest cells (NCCs) to coalesce into sensory ganglia and subsequent guidance of axonal projections from these newly formed ganglia. We have recently uncovered an essential role for Cas family members during retinal ganglion cell migration[13], yet our current understanding of Cas adaptor protein function during mammalian axon pathfinding in vivo is limited. One member of this family, p130Cas, has been proposed as a required downstream component of netrin-mediated commissural axon guidance in the chicken spinal cord[14]. These data provide insight into the interplay between adhesion to the substrate and axon fasciculation
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