Roles of Onecut factors in spinal dorsal interneuron and in sensory neuron development

Sensory experience is encoded by specific neurons located both in the peripheral and in the central nervous systems to integrate and elicit adequate responses. Sensory neurons, the cell bodies of which reside in dorsal root ganglia (DRG), relay input such as pain, temperature, itch, touch and limb and muscle length. This information is largely integrated and relayed in the spinal cord. During development, distinct neuronal types, including sensory neurons and dorsal interneurons (dIN), differentiate from progenitors into neurons characterized by distinct molecular identities, localizations and connectivity. However, the molecular mechanisms that control those processes remain incompletely characterized. Previous data obtained in our laboratory have shown that the Onecut (OC) transcription factors are present in sensory neurons and in several spinal dIN populations. This suggests that these factors could contribute to the regulation of the sensory neuron and spinal dIN development. My thesis goal is to study OC roles during these processes and to elucidate the underlying molecular mechanisms in the spinal cord. In this work, I provide evidence that the OC factors are necessary for proper diversification of dI5 interneurons and migration of early-born dIN populations. Moreover, I highlight that the OC factors control the expression of spinal Pou2f2. Using gain- or loss-of-function experiments, we show that Pou2f2 contributes to the regulation of dIN distribution. Also, I show that OC factors regulate early differentiation and segregation of distinct sensory subsets. Furthermore, OC are required for proper positioning and for normal projections of sensory neurons into the spinal cord or towards their peripheral targets. Thus, we uncover mechanisms of action of OC proteins in the regulation of spinal dIN development and OC involvement in sensory neuron differentiation, positioning and axonal projections during embryonic development.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201