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DKK1 expression is suppressed by miR-9 during induced dopaminergic differentiation of human trabecular meshwork

Elham Sadat Mirfazeli1, Ehsan Arefian2, Samad Nadri3

  • 1Developmental Biology Laboratory, School of Biology, College of Science, University of Tehran, Tehran, Iran.

Neuroscience Letters
|June 8, 2019
PubMed

Insights

MicroRNAs miR-9 and miR-101 regulate Wnt/β-catenin pathway activation during dopaminergic neuron differentiation by suppressing DKK1 expression. This study identifies a novel mechanism for controlling neural development using human trabecular meshwork stem cells.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Stem Cell Biology

Background:

  • The Wnt/β-catenin pathway is crucial for dopaminergic (DA) neuron differentiation.
  • DKK1, a Wnt pathway inhibitor, is regulated during brain development, but the mechanism remains unclear.

Purpose of the Study:

  • To investigate the molecular regulation of DKK1 during DA neuron differentiation.
  • To explore the role of microRNAs in modulating the Wnt/β-catenin pathway in this context.
  • To assess the utility of human trabecular meshwork mesenchymal stem cells (TM-MSCs) for in vitro DA neuron differentiation.

Main Methods:

  • In vitro differentiation of TM-MSCs into DA neuron-like cells.
  • Analysis of β-catenin nuclear accumulation and DKK1 transcript levels.
  • In silico prediction and experimental validation of microRNA targets (miR-9, miR-101) using overexpression and luciferase assays.

Main Results:

  • TM-MSCs successfully differentiated into DA neuron-like cells, showing increased Wnt/β-catenin activity.
  • DKK1 transcript levels significantly decreased during DA differentiation.
  • miR-9 and miR-101 were found to suppress DKK1 expression, with miR-9 directly targeting the 3'UTR.

Conclusions:

  • miR-9 and miR-101 play a significant role in reducing DKK1 expression during DA neuron differentiation.
  • These microRNAs contribute to the activation of the Wnt/β-catenin pathway essential for DA neuron development.
  • TM-MSCs represent a viable model for studying DA neuron differentiation mechanisms.
Keywords:
Mesenchymal stromal cellsMicroRNAsNeuronsTrabecular meshworkWnt signaling pathway

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