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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.

Lin28a/let-7 pathway modulates the Hox code via Polycomb regulation during axial patterning in vertebrates