about us

Research in the Deneris lab is aimed at understanding the gene regulatory networks that generate and maintain brain serotonin (5-HT) neurons. We have developed transgenic tools that enable experimental access to mouse serotonin neurons at different stages of life. Our genetic access provides an in vivo model with which to investigate the gene regulatory mechanisms that control the terminal differentiation, functional maturation and preservation of postmitotic 5-HT neurons. We discovered a network of 5-HT neuron transcription factors (TFs) that constitute a 5-HT gene regulatory network (5HT-GRN). Two key TFs in the 5HT-GRN, Pet1 and Lmx1b, preforms life-long functions in controlling the development and maintenance of 5-HT neurons. During embryonic life these TFs control chromatin accessibility for maturation of 5-HT neuron transcriptomes. Loss of Pet1 or Lmx1b results in severe deficits in brain 5-HT synthesis and numerous abnormal 5-HT modulated behaviors. These TFs also are essential for development of the long distance profusely arborized 5-HT axon architectures that deliver 5-HT throughout the brain and spinal cord, thus enabling expansive 5-HT neuromodulation. Adult-stage targeting of these TFs in 5-HT neurons causes progressive degeneration of 5-HT synapses and axons. Our work provides insight into the gene regulatory mechanisms that control postmitotic neuronal maturation during early life and adult-stage mechanisms that safeguard synapses and axons against degeneration. Read about our current projects and recent publications.