Transcriptional regulation of early cerebral cortex development
The cerebral cortex, the seat of our highest perceptual abilities and cognitive functions, is a highly organized structure composed of hundreds of different types of neurons. These neurons are assembled into different layers and distinct areas that process different types of sensory inputs, coordinate motor outputs or perform associational tasks. How cortical neurons are generated and assembled during embryonic development constitutes a major challenge in developmental neurosciences with important implications for our understanding of human neurodevelopmental diseases. Our recent work has shown that the zinc finger transcription factor Dmrt5 is required for the development of the caudomedial part of the cerebral cortex. Our current work aims to better understand Dmrt5 function and mode of action in cortical patterning and neurogenesis and the function of the related Dmrt3 and Dmrt4 genes that are expressed with Dmrt5 in cortical progenitors. To achieve this, we are using a range of functional assays such as the analysis of transgenic and conditional knockout mice and gene overexpression and knockdown by in utero electroporation. We also study their transcription targets using RNA-seq expression profiling and chromatin immunoprecipitation (ChIP-seq).
Epigenetic control of pain-sensing neuron differentiation and pain perception
The detection of noxious or damaging stimuli is an ancient process that alerts living organisms to environmental dangers. Harmful stimuli activate receptors on specific sensory neurons called nociceptors, which mediate information transfer via the spinal cord to higher order processing centers resulting in protective behaviors and awareness of pain. Erroneous activation of the pain-sensing system, as in chronic or neuropathic pain, represents a major health burden with insufficient treatment options. In a recent study on genetic disorders rendering individuals unable to feel pain, several mutations have been identified in a novel candidate disease-causing gene, PRDM12. Prdm12 encodes an evolutionarily conserved zinc finger transcription factor that is strongly expressed in the developing and adult nervous system, including in the dorsal root ganglia that contain the cell bodies of the sensory neurons. Recent work of the laboratory has shown that Prdm12 is required for sensory neurogenesis in the frog. We are currently studying in mammals its role and mecanism of action in nociceptor genesis and in pain perception in the adult, using genetic approaches in the mouse and the identification of its in vivo targets. Emerging evidences link epigenetic mechanisms to chronic and neuropathic pain. Therefore, our studies on Prdm12 could contribute to the development of novel therapeutic options for pain relief.