Journal Article

DKFZ-2026-00241

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The evolution of gene regulation in mammalian cerebellum development.

Sarropoulos, I. ; Sepp, M. ; Yamada, T. ; Schäfer, P. S. L. ; Trost, N. ; Schmidt, J. ; Schneider, C. ; Drummer, C. ; Mißbach, S. ; Taskiran, I. I. ; Hecker, N. ; Bravo González-Blas, C. ; Frömel, R. ; Joshi, P. K.DKFZ* ; Leushkin, E. ; Arnskötter, F.DKFZ* ; Leiss, K. ; Okonechnikov, K.DKFZ* ; Lisgo, S. ; Palkovits, M. ; Pääbo, S. ; Cardoso-Moreira, M. ; Kutscher, L.DKFZ* ; Behr, R. ; Pfister, S.DKFZ* ; Aerts, S. ; Kaessmann, H.

2026
Assoc. Washington, DC

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.

Keyword(s): Animals (MeSH) ; Cerebellum: embryology (MeSH) ; Cerebellum: growth & development (MeSH) ; Cerebellum: cytology (MeSH) ; Cerebellum: metabolism (MeSH) ; Humans (MeSH) ; Mice (MeSH) ; Gene Expression Regulation, Developmental (MeSH) ; Gene Regulatory Networks (MeSH) ; Evolution, Molecular (MeSH) ; Chromatin: metabolism (MeSH) ; Mammals: genetics (MeSH) ; Biological Evolution (MeSH) ; Chromatin

Note: #DKTKZFB26# / #NCTZFB26#

---

Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)
3. Entwicklungsbiolog. Ursprünge pädiatrischer Krebserkrankungen (B430)
4. Koordinierungsstelle NCT Heidelberg (HD02)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; Index Chemicus ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---