The evolution of gene regulation in mammalian cerebellum development
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Ioannis Sarropoulos Mari Sepp Tetsuya Yamada Philipp SL Schäfer Nils Trost Julia Schmidt Céline Schneider Charis Drummer Sophie Mißbach Ibrahim I Taskiran Nikolai Hecker Carmen Bravo González-Blas Robert Frömel Piyush Joshi Evgeny Leushkin Frederik Arnskötter Kevin Leiss Konstantin Okonechnikov Steven Lisgo Miklós Palkovits Svante Pääbo Margarida Cardoso Moreira Lena M Kutscher Rüdiger Behr Stefan M Pfister Stein Aerts Henrik Kaessmann
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Abstract
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.
Journal details
Journal
Science
Volume
391
Issue number
6784
Pages
eadw9154
Available online
Publication date
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Publisher website (DOI)
10.1126/science.adw9154
Europe PubMed Central
41610256
Pubmed
41610256
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The publication was previously a preprint.
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