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Updated: Apr 15, 2026
Differentiation of Mouse Embryonic Stem Cells into Cortical Interneuron Precursors
Published on: December 3, 2017
ERK1/2 is a key regulator of Fndc5 and PGC1α expression during neural differentiation of mESCs
S S Hosseini Farahabadi1, K Ghaedi2, F Ghazvini Zadegan3
1Cell and Molecular Biology Division, Biology Department, School of Sciences, University of Isfahan, Isfahan, Iran.
Abstract:
Fibronectin type III domain containing 5 (Fndc5) has already been distinguished to be involved in neural differentiation. However, cellular events of Fndc5 function are still ambiguous in the nervous system. One approach to shed light on duty of this protein in the nervous system is to find its cross-talks with various signaling pathways with defined characteristics and roles. Identification of the underlying molecular mechanism which controls Fndc5 expression and switches its activity up and down enables us to find out the Fndc5 functional map in the nervous system and other human body systems. Retinoic acid (RA) is a bio-small molecule which exerts its role as a neural inducer in the neurodevelopmental process of neural tube. RA up-regulates the expression of various genes involved in neural differentiation process via two distinct pathways: the genomic and the non-genomic. Our previous study has revealed that RA induces Fndc5 expression during neural differentiation process. In this study we have evaluated our hypothesis about the non-genomic up regulation of Fndc5 expression by RA. Interestingly we have identified that there is an association between ERK signaling pathway and Fndc5 expression. Furthermore, inhibition of this pathway by PD0325901 dramatically reduced Fndc5 mRNA level, while activating the pathway up-regulated Fndc5 transcription. In addition, it has been proven that ERK1/2 modulation via RA has more significant controlling effect on Fndc5 promoter rather than bFGF. This led us to conclude that RA enhances Fndc5 expression through a non-genomic pathway via the ERK signaling pathway.
Insights
Retinoic acid (RA) enhances Fibronectin type III domain containing 5 (Fndc5) expression via the ERK signaling pathway. This non-genomic mechanism is crucial for neural differentiation and understanding Fndc5 function in the nervous system.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Fibronectin type III domain containing 5 (Fndc5) is implicated in neural differentiation, but its precise cellular functions in the nervous system remain unclear.
- Understanding the molecular mechanisms controlling Fndc5 expression is key to elucidating its role in neural development and other biological systems.
Purpose of the Study:
- To investigate the non-genomic pathway through which retinoic acid (RA) up-regulates Fndc5 expression during neural differentiation.
- To identify the specific signaling pathways involved in RA-mediated Fndc5 induction.
Main Methods:
- Utilized retinoic acid (RA) as a neural inducer in a neurodevelopmental context.
- Investigated the association between the ERK signaling pathway and Fndc5 expression.
- Employed the ERK pathway inhibitor PD0325901 to assess its effect on Fndc5 mRNA levels.
- Compared the regulatory effect of ERK1/2 modulation by RA versus bFGF on the Fndc5 promoter.
Main Results:
- RA was found to up-regulate Fndc5 expression through a non-genomic mechanism.
- A significant association was identified between the ERK signaling pathway and Fndc5 expression.
- Inhibition of the ERK pathway with PD0325901 markedly decreased Fndc5 mRNA levels.
- Activation of the ERK pathway led to increased Fndc5 transcription, with ERK1/2 modulation by RA showing a stronger effect on the Fndc5 promoter than bFGF.
Conclusions:
- Retinoic acid (RA) enhances Fndc5 expression via a non-genomic pathway involving the ERK signaling cascade.
- The ERK signaling pathway plays a critical role in mediating the effects of RA on Fndc5 transcription during neural differentiation.
