The evolution of gene regulation in mammalian cerebellum development.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41610256.
- Also identified by DOI 10.1126/science.adw9154 and PMC identifier 7618896.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>THRB</i> expression in cerebellar progenitor cells. Collectively, our work reveals the shared and mammalian lineage-specific regulatory programs governing cerebellum development.
Medical subject headings
- Cerebellum
- Gene Expression Regulation, Developmental
- Gene Regulatory Networks
- Evolution, Molecular
- Mammals
- Biological Evolution