Back to Search
Start Over
A Zeb2-miR-200c loop controls midbrain dopaminergic neuron neurogenesis and migration
- Source :
- Communications Biology, Vol 1, Iss 1, Pp 1-11 (2018)
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- Zeb2 is a homeodomain transcription factor that plays pleiotropic functions during embryogenesis, but its role for midbrain dopaminergic (mDA) neuron development is unknown. Here we report that Zeb2 is highly expressed in progenitor cells in the ventricular zone of the midbrain floor plate and downregulated in postmitotic neuroblasts. Functional experiments show that Zeb2 expression in the embryonic ventral midbrain is dynamically regulated by a negative feedback loop that involves miR-200c. We also find that Zeb2 overexpression reduces the levels of CXCR4, NR4A2, and PITX3 in the developing ventral midbrain in vivo, resulting in migration and mDA differentiation defects. This phenotype was recapitulated by miR-200c knockdown, suggesting that the Zeb2-miR-200c loop prevents the premature differentiation of mDA progenitors into postmitotic cells and their migration. Together, our study establishes Zeb2 and miR-200c as critical regulators that maintain the balance between mDA progenitor proliferation and neurogenesis.
- Subjects :
- 0301 basic medicine
Neurogenesis
Medicine (miscellaneous)
Biology
General Biochemistry, Genetics and Molecular Biology
Cell biology
Midbrain
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
medicine.anatomical_structure
nervous system
lcsh:Biology (General)
Neuroblast
medicine
Homeobox
Neuron
Progenitor cell
General Agricultural and Biological Sciences
lcsh:QH301-705.5
030217 neurology & neurosurgery
Floor plate
Progenitor
Subjects
Details
- ISSN :
- 23993642
- Volume :
- 1
- Database :
- OpenAIRE
- Journal :
- Communications Biology
- Accession number :
- edsair.doi.dedup.....c3d8dd894503f9cec5afd1fcec5e0ab4