Fndc5 overexpression facilitated neural differentiation of mouse embryonic stem cells

Abstract

Fndc5 has been recently recognized as a myokine which could be cleaved and secreted into blood stream. It is termed as irisin with an important role in thermogenesis and energy homeostasis. Increased expression of Fndc5 has been reported upon retinoic acid treatment during neural differentiation and its knockdown decreased neural differentiation and neurite outgrowth. This study tries to evaluate the effect of Fndc5 overexpression on rate of neural differentiation in mouse. (Thus, transduced cell line of mouse embryonic stem cell with ability to express Fndc5 under Doxycycline treatment was established. Subsequently, the effect of overexpression of Fndc5 on different stages of neural differentiation was studied). Our study showed an increase enhancement in neuronal precursor markers and mature neuron markers upon overexpression of Fndc5, concluding that Fndc5 facilitates neural differentiation. This effect might be related to increased expression of BDNF following overexpression of Fndc5. Our findings are consistent with recent studies reporting a similar role for Fndc5 in proliferation of neural cells and increase in the expression of neurotrophins like BDNF.

FNDC5/Irisin – Their Role in the Nervous System and as a Mediator for Beneficial Effects of Exercise on the Brain

“…On the other hand, forced expression of FNDC5 during neuronal precursor formation from mouse embryonic stem cells increased mature neuronal markers (Map2, b-tubulinIII and Neurocan) and astrocyte marker (GFAP) and BDNF. However, overexpression of FNDC5 in undifferentiated mouse embryonic stem cells did not have these effects, indicating that FNDC5 supports neural differentiation rather than lineage commitment (Forouzanfar et al, 2015). Pharmacological doses of recombinant irisin increased cell proliferation in the mouse H19-7 hippocampal cell line (Moon et al, 2013).…”

Ketamine promotes the neural differentiation of mouse embryonic stem cells by activating mTOR

“…numerous genes serve an important role in the differentiation into neural stem cells (52,53). a recent study demonstrated that fibronectin type III domain-containing 5 facilitated neural differentiation by increasing the expression of brain derived neurotrophic factor (54). Zfhx1b gene expression has been confirmed to be notably upregulated via the fibroblast growth factor signaling pathway in meScs cultured in a permissive neural-inducing environment (19).…”

Can irisin be a linker between physical activity and brain function?

“…On the other hand, overexpression of Fndc5 significantly increases neural differentiation precursor markers and mature neuron markers. All these data suggest that FNDC5 may facilitate neural differentiation (21). Further studies (22) indicate that FNDC5 stimulates neural differentiation via the extracellular-signal-regulated kinase 1/2(ERK1/2) signaling pathway.…”