Department of Systems BioMedicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo, Japan; Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan
Kensuke Kataoka
Department of Systems BioMedicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan
Yoshiaki Ito
Department of Systems BioMedicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Research Core, Tokyo Medical and Dental University, Tokyo, Japan
Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo, Japan; Laboratory of Metabolism, National Institutes of Health, Bethesda, United States
Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo, Japan; Laboratory of Animal Regeneration Systemology, Meiji University, Kanagawa, Japan
Masaki Mori
Department of Systems BioMedicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Department of Medical Chemistry, Shiga University of Medical Science, Shiga, Japan
Satoru Takahashi
Department of Anatomy and Embryology, University of Tsukuba, Ibaraki, Japan
Department of Clinical Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
Shuji Takada
Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo, Japan
Hiroe Ueno-Kudoh
Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo, Japan; Reproduction Center, Yokohama City University, Yokohama, Japan
Department of Systems BioMedicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States
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.
