Abstract
ABSTRACTDuring the development of the peripheral nervous system, a subgroup of neural crest cells migrate away from the neural tube and coalesce into clusters of sensory neurons (ganglia). Mechanisms involved in the formation of the dorsal root ganglia (DRG) from neural crest cells are currently unclear. Mice carrying mutations in Cxcr4, which is known to control neural crest migration, exhibit malformed DRG. In order to investigate this phenomenon, we modelled sensory neuron differentiation in vitro by directing the differentiation of human induced pluripotent stem cells into sensory neurons under SDF1 (agonist), AMD3100 (antagonist) or control conditions. There we could show a marked effect on the clustering activity of the neurons in vitro, suggesting that CXCR4 signalling is involved in facilitating DRG condensation.
Highlights
The characterization of molecules that direct the development of the nervous system is vital for advances in neuroregeneration
When looking at the sensory nervous system, sensory neuron cell bodies are organised into clusters adjacent to the spinal cord known as dorsal root ganglia (DRG)
The Cxcr4-null mouse shows small fragmented DRG based on nociceptor cell staining, indicating a possible role directing their formation (Belmadani et al, 2005). Based upon these previously reported effects on mouse DRG formation, we modelled the development of human nociceptors in vitro and examined the effects of SDF1 and AMD3100 on both their differentiation and morphology
Summary
The characterization of molecules that direct the development of the nervous system is vital for advances in neuroregeneration. When looking at the sensory nervous system, sensory neuron cell bodies are organised into clusters adjacent to the spinal cord known as dorsal root ganglia (DRG). The exact signalling mechanisms orchestrating their condensation from neural crest-derived sensory neuron precursors are unknown. Progress on this front has been made examining mutants that display aberrant DRG formation in vivo such as a failure to condense into proper ganglia in the Cxcr4−/− mouse (Belmadani et al, 2005). Differentiation into a (non-placode) sensory neural lineage is more complex due to having first to pass through the transient neural crest stage before reaching the neural precursors and terminally differentiated sensory neurons (Lee et al, 2007). In a 2009 study by Chambers et al, high efficiency neural induction was accomplished by inhibiting both the
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