Ebf3-miR218 regulation is involved in the development of dopaminergic neurons

• Published in: Brain research Vol. 1587; pp. 23 - 32
• Main Authors: Baek, Soonbong, Choi, Hwan, Kim, Jongpil
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 31.10.2014; Elsevier
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; DEAD-box RNA Helicases - deficiency; DEAD-box RNA Helicases - physiology; Dopaminergic neurons; Dopaminergic Neurons - cytology; Ebf3; Feedback, Physiological; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gene Expression Regulation, Developmental; Mesencephalon - cytology; Mice; Mice, Knockout; Micro RNA; MicroRNAs; Nerve Tissue Proteins - analysis; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Neurogenesis - genetics; Neurology; Recombinant Fusion Proteins - metabolism; Ribonuclease III - deficiency; Ribonuclease III - physiology; Transcription Factors; Transduction, Genetic; Tyrosine 3-Monooxygenase - analysis; Vertebrates: nervous system and sense organs; Dopaminergic neurons; Ebf3; Micro RNA; Development; Gene silencing; Dopaminergic neuron
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2014.08.059

Abstract The development of midbrain dopaminergic (DA) neurons is a complex process that requires the precise spatial and temporal expression of numerous genes. Here, we report that Ebf3, a transcription factor, plays a critical role in the terminal development of DA neurons. We found a specific upregulation of Ebf3 in Dicer knockout midbrain DA neurons and dynamic patterns of Ebf3 expression during the development of DA neurons. We further demonstrated that the overexpression of Ebf3 at the neural precursor stage of embryonic stem (ES) differentiation induces a significant increase in the number of TH+ DA neurons, whereas the suppression of Ebf3 leads to significant reduction in the development of TH+ DA neurons. Additionally, we found that Ebf3 is a candidate target for miR218 during DA neuronal development, such that the regulation of Ebf3 expression by miR218 controls the terminal differentiation of DA neurons. Thus, our data suggest that complex transcription factor–miRNA regulation is critical for the development of midbrain DA neurons.