First Author | Delgado I | Year | 2021 |
Journal | Nat Commun | Volume | 12 |
Issue | 1 | Pages | 3086 |
PubMed ID | 34035267 | Mgi Jnum | J:306114 |
Mgi Id | MGI:6713962 | Doi | 10.1038/s41467-021-23373-9 |
Citation | Delgado I, et al. (2021) Control of mouse limb initiation and antero-posterior patterning by Meis transcription factors. Nat Commun 12(1):3086 |
abstractText | 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. |