RT Journal Article
T1 Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development
A1 Dvoretskova, Elena
A1 Ho, May C.
A1 Kittke, Volker
A1 Neuhaus, Florian
A1 Vitali, Ilaria
A1 Lam, Daniel D.
A1 Delgado Carceller, Irene
A1 Feng, Chao
A1 Torres, Miguel
A1 Winkelmann, Juliane
A1 Mayer, Christian
AB The mammalian telencephalon contains distinct GABAergic projection neuron and interneuron types, originating in the germinal zone of the embryonic basal ganglia. How genetic information in the germinal zone determines cell types is unclear. Here we use a combination of in vivo CRISPR perturbation, lineage tracing and ChIP–sequencing analyses and show that the transcription factor MEIS2 favors the development of projection neurons by binding enhancer regions in projection-neuron-specific genes during mouse embryonic development. MEIS2 requires the presence of the homeodomain transcription factor DLX5 to direct its functional activity toward the appropriate binding sites. In interneuron precursors, the transcription factor LHX6 represses the MEIS2–DLX5-dependent activation of projection-neuron-specific enhancers. Mutations of Meis2 result in decreased activation of regulatory enhancers, affecting GABAergic differentiation. We propose a differential binding model where the binding of transcription factors at cis-regulatory elements determines differential gene expression programs regulating cell fate specification in the mouse ganglionic eminence.
PB Springer
SN 1097-6256
YR 2024
FD 2024
LK https://hdl.handle.net/20.500.14352/119111
UL https://hdl.handle.net/20.500.14352/119111
LA eng
NO Dvoretskova, E., Ho, M.C., Kittke, V. et al. Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development. Nat Neurosci 27, 862–872 (2024). https://doi.org/10.1038/s41593-024-01611-9
NO This work was supported by the Max Planck Society, the European Research Council (ERC) under the European Union Horizon 2020 Research and Innovation program (ERC-2018-STG, grant agreement no. 803984, GIDE; to C.M.), the European Commission (ERA-NET NEURON no. 01EW1605) and EXC 2145 SyNergy (390857198). Open access funding provided by Max Planck Society..
NO Max Planck Society
NO European Commission
DS Docta Complutense
RD 18 dic 2025