Igf1R/InsR function is required for axon extension and corpus callosum formation

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Biology

Background:

• Neuronal polarity and axon formation are critical early steps in nervous system development.
• Extrinsic signals initiating axon formation are less understood than intrinsic mechanisms.
• Insulin-like growth factor 1 (Igf1) is a candidate extrinsic signal, acting via Igf1 receptors (Igf1R) and insulin receptors (InsR).

Purpose of the Study:

• To investigate the in vivo role of Igf1R and InsR in cortical development and axon formation.
• To analyze the function of Igf1R and InsR, which may act redundantly, using conditional cortex-specific knockout mice deficient in both.

Main Methods:

• Generation and analysis of conditional cortex-specific knockout mice lacking both Igf1r and Insr.
• Examination of embryonic brain development, including cortical organization and axon formation.
• In vitro culture of cortical and hippocampal neurons from knockout embryos to assess axon extension.

Main Results:

• Igf1R/InsR signaling is essential for normal embryonic hippocampus and cingulate cortex development, but not the lateral cortex.
• In the cingulate cortex, knockout embryos showed reduced intermediate progenitors, fewer deep layer neurons, and absent corpus callosum.
• Cortical organization and axon formation were not impaired in knockout embryos in vivo, but cultured neurons exhibited significantly reduced axon length.

Conclusions:

• Igf1R/InsR signaling plays a region-specific role in brain development.
• This signaling pathway promotes axon growth but is not essential for neuronal polarization or migration during brain development.