ABSTRACT
Neurons in the peripheral nervous system (PNS) display a higher capacity to regenerate after injury than those in the central nervous system, suggesting cell specific transcriptional modules underlying axon growth and inhibition. We report a systems biology based search for PNS specific transcription factors (TFs). Messenger RNAs enriched in dorsal root ganglion (DRG) neurons compared to cerebellar granule neurons (CGNs) were identified using subtractive hybridization and DNA microarray approaches. Network and transcription factor binding site enrichment analyses were used to further identify TFs that may be differentially active. Combining these techniques, we identified 32 TFs likely to be enriched and/or active in the PNS. Twenty-five of these TFs were then tested for an ability to promote CNS neurite outgrowth in an overexpression screen. Real-time PCR and immunohistochemical studies confirmed that one representative TF, STAT3, is intrinsic to PNS neurons, and that constitutively active STAT3 is sufficient to promote CGN neurite outgrowth.
Subject(s)
Neurons/physiology , Peripheral Nervous System/physiology , Transcription Factors/metabolism , Transcription, Genetic , Animals , Cerebellum/cytology , Ganglia, Spinal/cytology , Gene Expression Profiling/methods , Mice , Mice, Inbred C57BL , Microarray Analysis/methods , Neurons/cytology , Nucleic Acid Hybridization/methods , RNA, Messenger/genetics , RNA, Messenger/metabolism , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Signal Transduction/physiology , Transcription Factors/geneticsABSTRACT
Central serotonergic signaling influences many physiological processes, but a requirement for reproductive success has not been demonstrated. Using mouse dams with a specific disruption in serotonin neuron development, we found that serotonergic function is required for the nurturing and survival of offspring. Full rescue of survival depended on the mother's expression level of the upstream serotonergic transcriptional cascade. Thus, intrinsic transcriptional programming of maternal serotonergic activity determines the quality of nurturing and whether or not the organism survives.