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GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation

Antonela Bonafina1, Paula Aldana Fontanet1, Gustavo Paratcha1

  • 1Division of Molecular and Cellular Neuroscience, Institute of Cell Biology and Neuroscience (IBCN)-CONICET-UBA, School of Medicine, University of Buenos Aires (UBA), Buenos Aires CP 1121, Argentina.

Stem Cell Reports
|February 27, 2018
PubMed

Insights

Glial cell line-derived neurotrophic factor (GDNF) and its receptor GFRα1 regulate brain development. This signaling pathway inhibits neural precursor self-renewal and promotes neuronal differentiation, crucial for cortical development.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Signaling

Background:

  • Cortical neural precursor (CNP) proliferation and differentiation balance is critical for proper brain development.
  • Fibroblast growth factor 2 (FGF2) is known to promote the self-renewal of CNPs.
  • The role of GDNF/GFRα1 signaling in cortical development requires further elucidation.

Purpose of the Study:

  • To investigate the expression and function of GDNF and GFRα1 during cortical neurogenesis.
  • To determine the effect of GDNF/GFRα1 signaling on the proliferation and differentiation of CNPs.
  • To analyze the impact of GFRα1 deficiency on cortical development in vivo.

Main Methods:

  • Analysis of GDNF and GFRα1 expression in the developing mouse neocortex.
  • In vitro studies using cultured mouse CNPs treated with GDNF and FGF2.
  • Genetic manipulation using GFRα1-deficient mice to assess in vivo effects on cortical development.

Main Results:

  • GDNF and GFRα1 are expressed in the neocortex during neurogenesis.
  • The GDNF/GFRα1 complex inhibits FGF2-induced self-renewal of CNPs, promoting neuronal differentiation.
  • GFRα1 deficiency in mice leads to increased cell proliferation and impaired dendrite development in the cortex.

Conclusions:

  • GDNF/GFRα1 signaling is essential for regulating the balance between proliferation and differentiation of cortical progenitors.
  • This pathway plays a critical role in controlling the cell cycle status and differentiation trajectory of neural precursors.
  • Dysregulation of GDNF/GFRα1 signaling can lead to aberrant cortical development.
Keywords:
GDNFGFRα1cortical precursorsneuronal differentiationpostmitotic neuronsproliferation

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