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Srebf1 Controls Midbrain Dopaminergic Neurogenesis
Enrique M Toledo1, Shanzheng Yang1, Daniel Gyllborg1
1Laboratory for Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Biomedicum, Solnavägen 9, 17177 Stockholm, Sweden.
Cell Reports
|May 7, 2020
Summary
Liver X receptors (LXRs) regulate midbrain dopaminergic (mDA) neurogenesis. Sterol regulatory element binding protein 1 (SREBP1) is identified as a key transcription factor required for this process.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Liver X receptors (LXRs) are known regulators of midbrain dopaminergic (mDA) neurogenesis and differentiation.
- The precise molecular mechanisms underlying LXR control of these processes are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms and transcriptional networks by which LXRs control mDA neurogenesis.
- To identify key transcription factors involved in LXR-mediated mDA development.
Main Methods:
- Combined transcriptome and chromatin immunoprecipitation sequencing (ChIP-seq) analysis of midbrain cells following LXR activation.
- Bioinformatic analysis to identify transcriptional networks.
- In vitro and in vivo loss- and gain-of-function experiments.
Main Results:
- Sterol regulatory element binding protein 1 (SREBP1), a basic helix-loop-helix transcription factor, was identified as a crucial regulator.
- SREBP1 is part of a proneural transcription factor cluster in radial glia and regulates factors like Foxa2.
- Srebf1 was found to be both necessary and sufficient for mDA neurogenesis.
Conclusions:
- SREBP1 is a central molecular player in the regulation of midbrain dopaminergic neurogenesis.
- This study reveals a novel role for SREBP1 in neuronal development within the midbrain.
