Science (New York, N.Y.) · 2026
The evolution of gene regulation in mammalian cerebellum development.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Sarropoulos Ioannis, Sepp Mari, Yamada Tetsuya, Schäfer Philipp S L, Trost Nils, Schmidt Julia, Schneider Céline, Drummer Charis, Mißbach Sophie, Taskiran Ibrahim I, Hecker Nikolai, Bravo González-Blas Carmen, Frömel Robert, Joshi Piyush, Leushkin Evgeny, Arnskötter Frederik, Leiss Kevin, Okonechnikov Konstantin, Lisgo Steven, Palkovits Miklós, Pääbo Svante, Cardoso-Moreira Margarida, Kutscher Lena M, Behr Rüdiger, Pfister Stefan M, Aerts Stein, Kaessmann Henrik
Аннотация
Gene regulatory changes are considered major drivers of evolutionary innovations, including the cerebellum's expansion during human evolution, yet they remain largely unexplored. In this study, we combined single-nucleus measurements of gene expression and chromatin accessibility from six mammals (human, bonobo, macaque, marmoset, mouse, and opossum) to uncover conserved and diverged regulatory networks in cerebellum development. We identified core regulators of cell identity and developed sequence-based models that revealed conserved regulatory codes. By predicting chromatin accessibility across 240 mammalian species, we reconstructed the evolutionary histories of human cis-regulatory elements, identifying sets associated with positive selection and gene expression changes, including the recent gain of THRB expression in cerebellar progenitor cells. Collectively, our work reveals the shared and mammalian lineage-specific regulatory programs governing cerebellum development.