Delgado, IreneGiovinazzo, GiovannaTemiño, SusanaGauthier, YvesBalsalobre, AurelioDrouin, JacquesTorres, Miguel2022-12-012022-12-012021-05-25Nat Commun. 2021 May 25;12(1):3086.http://hdl.handle.net/20.500.12105/15251Meis1 and Meis2 are homeodomain transcription factors that regulate organogenesis through cooperation with Hox proteins. Elimination of Meis genes after limb induction has shown their role in limb proximo-distal patterning; however, limb development in the complete absence of Meis function has not been studied. Here, we report that Meis1/2 inactivation in the lateral plate mesoderm of mouse embryos leads to limb agenesis. Meis and Tbx factors converge in this function, extensively co-binding with Tbx to genomic sites and co-regulating enhancers of Fgf10, a critical factor in limb initiation. Limbs with three deleted Meis alleles show proximal-specific skeletal hypoplasia and agenesis of posterior skeletal elements. This failure in posterior specification results from an early role of Meis factors in establishing the limb antero-posterior prepattern required for Shh activation. Our results demonstrate roles for Meis transcription factors in early limb development and identify their involvement in previously undescribed interaction networks that regulate organogenesis.engVoRhttp://creativecommons.org/licenses/by/4.0/AnimalsBasic Helix-Loop-Helix Transcription FactorsBody PatterningDNA-Binding ProteinsFibroblast Growth Factor 10Hedgehog ProteinsHomeodomain ProteinsLimb BudsMice, KnockoutMice, TransgenicModels, GeneticMyeloid Ecotropic Viral Integration Site 1 ProteinNeoplasm ProteinsT-Box Domain ProteinsTranscription FactorsTranscriptional ActivationAtribución 4.0 Internacional34035267121308610.1038/s41467-021-23373-92041-1723Nature communicationsopen access