Serping1/C1 Inhibitor Affects Cortical Development in a Cell Autonomous and Non-cell Autonomous Manner

Area of Science:

• Neuroscience
• Immunology
• Developmental Biology

Background:

• Radial neuronal migration is crucial for brain development.
• Existing knowledge on neuronal migration regulation primarily focuses on intracellular factors.
• Non-cell autonomous mechanisms remain less understood.

Purpose of the Study:

• To identify non-cell autonomous regulators of radial neuronal migration.
• To investigate the role of Serping1 (C1 inhibitor) and the complement cascade in this process.

Main Methods:

• Unbiased screening to detect differentially expressed genes.
• Serping1 knockdown/knockout in mouse models.
• In utero electroporation to assess cell migration and polarity.
• Functional rescue experiments using complement pathway components and receptor agonists.

Main Results:

• Serping1 knockdown/knockout impaired neuronal stem cell proliferation and migration in mice.
• In utero electroporation of Serping1 siRNA caused non-cell autonomous migration delays and affected cellular polarity.
• Complement pathway activation was confirmed, with C5a receptors playing a key role in rescuing migration defects.

Conclusions:

• The complement pathway, regulated by Serping1, is involved in neuronal migration.
• Serping1 influences brain development through non-cell autonomous mechanisms.
• This study reveals an unconventional role for the complement system in neurodevelopment.