2. Academic Validation
  3. The growth factor EPIREGULIN promotes basal progenitor cell proliferation in the developing neocortex

The growth factor EPIREGULIN promotes basal progenitor cell proliferation in the developing neocortex

  • EMBO J. 2024 Mar 21. doi: 10.1038/s44318-024-00068-7.
Paula Cubillos 1,  Nora Ditzer 1,  Annika Kolodziejczyk 1,  Gustav Schwenk 1,  Janine Hoffmann 1,  Theresa M Schütze 1,  Razvan P Derihaci 2 3,  Cahit Birdir 2 4,  Johannes Em Köllner 5,  Andreas Petzold 6,  Mihail Sarov 5,  Ulrich Martin 7 8,  Katherine R Long 9 10,  Pauline Wimberger 2 3,  Mareike Albert 11
Affiliations

Affiliations

  • 1 Center for Regenerative Therapies TU Dresden, TUD Dresden University of Technology, 01307, Dresden, Germany.
  • 2 Department of Gynecology and Obstetrics, TU Dresden, 01307, Dresden, Germany.
  • 3 National Center for Tumor Diseases, 01307, Dresden, Germany.
  • 4 Center for feto/neonatal Health, TU Dresden, 01307, Dresden, Germany.
  • 5 Max Planck Institute of Molecular Cell Biology and Genetics, 01307, Dresden, Germany.
  • 6 DRESDEN-concept Genome Center, Center for Molecular and Cellular Bioengineering, TUD Dresden University of Technology, 01307, Dresden, Germany.
  • 7 Leibniz Research Laboratories for Biotechnology and Artificial Organs, Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625, Hannover, Germany.
  • 8 REBIRTH-Cluster of Excellence, Hannover, Germany.
  • 9 Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE1 1UL, United Kingdom.
  • 10 MRC Centre for Neurodevelopmental Disorders, King's College London, London, SE1 1UL, United Kingdom.
  • 11 Center for Regenerative Therapies TU Dresden, TUD Dresden University of Technology, 01307, Dresden, Germany. [email protected].
PMID: 38514807 DOI: 10.1038/s44318-024-00068-7
Abstract

Neocortex expansion during evolution is linked to higher numbers of neurons, which are thought to result from increased proliferative capacity and neurogenic potential of basal progenitor cells during development. Here, we show that EREG, encoding the growth factor Epiregulin, is expressed in the human developing neocortex and in gorilla cerebral organoids, but not in the mouse neocortex. Addition of Epiregulin to the mouse neocortex increases proliferation of basal progenitor cells, whereas EREG ablation in human cortical organoids reduces proliferation in the subventricular zone. Treatment of cortical organoids with Epiregulin promotes a further increase in proliferation of gorilla but not of human basal progenitor cells. Epiregulin competes with the epidermal growth factor (EGF) to promote proliferation, and inhibition of the EGF receptor abrogates the EPIREGULIN-mediated increase in basal progenitor cells. Finally, we identify putative cis-regulatory elements that may contribute to the observed inter-species differences in EREG expression. Our findings suggest that species-specific regulation of Epiregulin expression may contribute to the increased neocortex size of primates by providing a tunable pro-proliferative signal to basal progenitor cells in the subventricular zone.

Keywords

Cortical Organoid; Gene Regulation; Human Neurogenesis; Neocortex Evolution; Neural Progenitor Cell.

Figures
Products