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Patterned cPCDH expression regulates the fine organization of the neocortex
Xiaohui Lv1,2,3, Shuo Li1,2,4, Jingwei Li5
1IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, China.
Nature
|December 8, 2022
Summary
Clustered protocadherins (cPCDHs) regulate neuronal arrangement and connectivity in the mouse neocortex. Their diverse expression patterns guide spatial organization and synaptic connections of excitatory neurons.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- The neocortex contains diverse neurons forming complex circuits for brain function.
- Cell-surface molecules are crucial for neuronal identity and organization.
- Mechanisms governing precise neocortical neuronal organization are not fully understood.
Purpose of the Study:
- To investigate the role of clustered protocadherins (cPCDHs) in neocortical excitatory neuron organization.
- To understand how cPCDH expression patterns influence spatial arrangement and synaptic connectivity.
Main Methods:
- Single-cell RNA-sequencing analysis
- Progenitor lineage labeling
- Mosaic functional analysis
Main Results:
- cPCDH gene expression is diverse but patterned in neocortical excitatory neurons, linked to origin and position.
- Reduced cPCDH function leads to lateral clustering of related neurons and increased synaptic connectivity.
- Overexpression of a single cPCDH isoform causes lateral dispersion and decreased synaptic connectivity.
Conclusions:
- Patterned cPCDH expression is essential for the fine spatial and functional organization of individual neocortical excitatory neurons.
- cPCDHs mediate cell-adhesion and signaling critical for neuronal circuit formation.
