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Publication : <i>Lin28a/let-7</i> pathway modulates the <i>Hox</i> code via <i>Polycomb</i> regulation during axial patterning in vertebrates.

First Author  Sato T Year  2020
Journal  Elife Volume  9
PubMed ID  32479258 Mgi Jnum  J:290220
Mgi Id  MGI:6442028 Doi  10.7554/eLife.53608
Citation  Sato T, et al. (2020) Lin28a/let-7 pathway modulates the Hox code via Polycomb regulation during axial patterning in vertebrates. Elife 9:e53608
abstractText  The body plan along the anteroposterior axis and regional identities are specified by the spatiotemporal expression of Hox genes. Multistep controls are required for their unique expression patterns; however, the molecular mechanisms behind the tight control of Hox genes are not fully understood. In this study, we demonstrated that the Lin28a/let-7 pathway is critical for axial elongation. Lin28a(-/-) mice exhibited axial shortening with mild skeletal transformations of vertebrae, which were consistent with results in mice with tail bud-specific mutants of Lin28a. The accumulation of let-7 in Lin28a(-/-) mice resulted in the reduction of PRC1 occupancy at the Hox cluster loci by targeting Cbx2. Consistently, Lin28a loss in embryonic stem-like cells led to aberrant induction of posterior Hox genes, which was rescued by the knockdown of let-7. These results suggest that the Lin28/let-7 pathway is involved in the modulation of the 'Hox code' via Polycomb regulation during axial patterning.
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