Résumé :
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Communication n° 680. Several classes of neurons are generated from neuronal progenitors along the dorso-ventral axis of the spinal cord and are defined according to the expression of specific gene combinations. GATA2, a zinc finger transcription factor, participates to the specification of V2 interneurons, a subset of neurons adjacent to motoneurons. V2 interneurons are divided in two subclasses, V2A and V2B, which are equally distributed in the ventral spinal cord. We have investigated the potential role of GATA2 in V2 interneurons dichotomy and will subsequently characterize their function. By loss- and gain-of-function experiments in mouse and chick embryos respectively, we have characterized other genes interacting with GATA2 during V2 specification. In the spinal cord, V2A interneurons are Lim3+, Chx10+ and Ngn2+, while V2B interneurons are Lim1/2+, GATA3+ and Mash1+. Loss-of-function of GATA2, Mash1 or Ngn2 affects V2 interneuron differentiation. In addition, GATA2 gain-of-function experiments have demonstrated that GATA2 induces Mash1, Lim1/2 and GATA3 (V2B interneurons) but represses Ngn2 and Lim3 (V2A interneurons). These results provide evidence that GATA2 participates to the differentiation of V2 interneurons and suggest that their dichotomy probably results from an asymmetric differentiation, which could involve Ngn2 and Mash1. Furthermore, this approach allowed to show that GATA2 inhibits motoneuron differentiation. In conclusion GATA2 acts as a specification gene by promoting V2 interneuron differentiation at the expense of motoneurons (repression of motoneuronal markers). We will further characterize these neurons and their function, which has not yet been established. Transgenic mice which permanently express LacZ in V2 interneurons, from the precursor to the adult stage will be used. This will enable us to understand how the V2 interneuron function is integrated within the locomotor circuitry (neuron targets and neurotransmission).
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