Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/15251
Title
Control of mouse limb initiation and antero-posterior patterning by Meis transcription factors.
Author(s)
Delgado, Irene CNIC | Giovinazzo, Giovanna CNIC | Temiño, Susana | Gauthier, Yves | Balsalobre, Aurelio | Drouin, Jacques | Torres, Miguel CNIC
Date issued
2021-05-25
Citation
Nat Commun. 2021 May 25;12(1):3086.
Language
Inglés
Document type
journal article
Abstract
Meis1 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.
MESH
Animals | Basic Helix-Loop-Helix Transcription Factors | Body Patterning | DNA-Binding Proteins | Fibroblast Growth Factor 10 | Hedgehog Proteins | Homeodomain Proteins | Limb Buds | Mice, Knockout | Mice, Transgenic | Models, Genetic | Myeloid Ecotropic Viral Integration Site 1 Protein | Neoplasm Proteins | T-Box Domain Proteins | Transcription Factors | Transcriptional Activation
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