Wiring the Brain by Clustered Protocadherin Neural Codes

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• The human brain forms over a million new synaptic connections per second in early life.
• Complex neuronal circuits require molecular tags for unique neuronal identification (self vs. non-self).
• Clustered protocadherin (Pcdh) genes encode diverse cell-surface proteins, making them candidates for these identity tags.

Purpose of the Study:

• To describe the adaptive evolution, genomic structure, and expression regulation of clustered Pcdh genes.
• To investigate the 3-D architectural and biophysical mechanisms generating Pcdh diversity.
• To explore the role of Pcdhs as neural codes in the brain.

Main Methods:

• Analysis of clustered Pcdh gene evolution and genomic organization.
• Investigation of Pcdh gene expression regulation.
• Examination of 3-D structural and biophysical properties of Pcdh molecules.

Main Results:

• Clustered Pcdhs exhibit adaptive evolution and a complex genomic structure.
• Specific regulatory mechanisms control Pcdh expression.
• Emerging evidence points to 3-D architecture and biophysics generating Pcdh diversity for neural coding.

Conclusions:

• Clustered Pcdhs are crucial for establishing neuronal identity codes.
• The diversity of Pcdh cell-surface assemblies is generated through sophisticated mechanisms.
• Pcdhs play a fundamental role in the formation of complex neural circuits.