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Cytokinin signalling, mediated by the CRE1 receptor, plays a crucial role in symbiotic nodule and lateral root formation in Medicago truncatula, a model for legume research (Gonzalez-Rizzo et al., 2006; Plet et al., 2011). In seed plants, members of the KNOX homeodomain transcription factor family control multiple hormonal pathways in the determination of cell fate and organ formation at the shoot apical meristem, including cytokinin biosynthesis (Di Giacomo et al., 2013). In M. truncatula, most KNOXs express in roots where rhizobia can induce symbiotic nodules that develop through a persistent meristem. Within the framework of a bilateral Scientific Cooperation between CNR (IT) and CNRS (FR), we are investigating the role of KNOX genes in cytokinin-mediated symbiotic nodule organogenesis in M. truncatula. Among several KNOXs (MtKNOXs) expressed in root (Di Giacomo et al., 2008), we identified three cytokinin-regulated genes that may act downstream of the CRE1-dependent cytokinin pathway. The three MtKNOX genes identified are homologous of the Arabidopsis thaliana KNAT6 (MtKNOX7), KNAT-M (MtKNATM/FCL1) and KNAT3 (MtKNOX3). Preliminary results suggested that MtKNOX3 and two additional MtKNOX3-like genes are preferentially expressed in zone I and II of the symbiotic nodule, corresponding to nodule meristem and prefixation zone. Functional studies involving the analysis of mutants and Agrobacterium rhizogenes-mediated M. truncatula roots that misexpress MtKNOX genes have been carried out to assess MtKNOXs role in cytokinin-mediated symbiotic nodule organogenesis.