A Developmental Switch in the Response of DRG Neurons to ETS Transcription Factor Signaling

A Developmental Switch in the Response of DRG Neurons to ETS Transcription Factor Signaling

May 2005 | Volume 3 | Issue 5 | e159 | Simon Hippenmeyer, Eline Vrieseling, Markus Sigrist, Thomas Portmann, Celia Laengle, David R. Ladle, Silvia Arber
This study investigates the role of ETS transcription factors in the differentiation of dorsal root ganglion (DRG) neurons. Two ETS transcription factors, Er81 and Pea3, are induced by target-derived factors in DRG sensory and spinal motor neurons, controlling late aspects of neuronal differentiation such as target invasion and branching. The authors show that the late onset of ETS gene expression is essential for normal sensory neuron differentiation. Genetic evidence in mice indicates that precocious ETS expression in DRG sensory neurons disrupts axonal projections, the acquisition of terminal differentiation markers, and their dependence on neurotrophic support. The findings suggest that DRG sensory neurons exhibit a temporal developmental switch, with distinct responses to ETS transcription factor signaling at different stages of neuronal maturation. The study also demonstrates that EWS-Pea3, a fusion protein of the EWS gene and the Pea3 domain, can replace Er81 function in controlling Ia afferent projections into the spinal cord. Precocious expression of EWS-Pea3 in DRG neurons leads to axonal projection defects and neurotrophin-independent survival and neurite outgrowth. These results highlight the importance of temporally controlled activation of transcriptional programs in neuronal maturation and circuit assembly.This study investigates the role of ETS transcription factors in the differentiation of dorsal root ganglion (DRG) neurons. Two ETS transcription factors, Er81 and Pea3, are induced by target-derived factors in DRG sensory and spinal motor neurons, controlling late aspects of neuronal differentiation such as target invasion and branching. The authors show that the late onset of ETS gene expression is essential for normal sensory neuron differentiation. Genetic evidence in mice indicates that precocious ETS expression in DRG sensory neurons disrupts axonal projections, the acquisition of terminal differentiation markers, and their dependence on neurotrophic support. The findings suggest that DRG sensory neurons exhibit a temporal developmental switch, with distinct responses to ETS transcription factor signaling at different stages of neuronal maturation. The study also demonstrates that EWS-Pea3, a fusion protein of the EWS gene and the Pea3 domain, can replace Er81 function in controlling Ia afferent projections into the spinal cord. Precocious expression of EWS-Pea3 in DRG neurons leads to axonal projection defects and neurotrophin-independent survival and neurite outgrowth. These results highlight the importance of temporally controlled activation of transcriptional programs in neuronal maturation and circuit assembly.
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