Units

Developmental Genetics

Person in charge of the Unit : Oui

Our unit is studying vertebrate nervous system development, focusing on the molecular mechanisms that control the transition from neural stem cell to neurons in the developing vertebrate nervous system.  We focus on some transcription factors to probe the molecular mechanisms controling neural progenitor maintenance, differentiation, and the generation of neuronal diversity in the developing telencephalon and sensory ganglia. We use for our work the Xenopus embryo, which offers many advantages for in vivo gene function analysis during early embryonic development. Functional assays in Xenopus are complemented by  gain- and loss-of-function by electroporation in chick embryos and genetic knockouts in the mouse, to gain fuller understanding of gene action and their normal requirements in the developing embryo. Gaining insight into the mechanisms driving the differentiation of neural stem cells into specific types of neurons  will help to understand neurological disorders and to devise novel therapeutic strategies.

Projetcs

Molecular mechanisms of sensory neurogenesis 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. Pain disorders are associated with many human diseases and constitute a burden in human societies. In a recent study on CIP (Congenital Insensitivity to 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. A 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 genenesis and in pain perception in the adult, using genetic approaches in the mouse and the identification of its in vivo targets (using RNA-seq and ChIP-seq). 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.

Studying the genetic programs that control cerebral cortex development

The cerebral cortex is composed of hundreds of different types of neurons assembled in a highly organized structure. How cortical neurons are generated during embryonic development constitutes a major challenge in developmental neurosciences with implications for neural diseases. Our recent work has shown that the zinc finger transcription factor Dmrt5 and Dmrt3 are required for the development of the caudomedial part of the cerebral cortex. Our current work aims to better understand their function and mode of action in cortical patterning and neurogenesis.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 electroporation in utero. We also study their transcription targets using expression profiling and chromatin immunoprecipitation (ChIP-seq) experiments.