Patterned cPCDH expression regulates the fine organization of the neocortex Journal Article
| Authors: | Lv, X.; Li, S.; Li, J.; Yu, X. Y.; Ge, X.; Li, B.; Hu, S.; Lin, Y.; Zhang, S.; Yang, J.; Zhang, X.; Yan, J.; Joyner, A. L.; Shi, H.; Wu, Q.; Shi, S. H. |
| Article Title: | Patterned cPCDH expression regulates the fine organization of the neocortex |
| Abstract: | The neocortex consists of a vast number of diverse neurons that form distinct layers and intricate circuits at the single-cell resolution to support complex brain functions1. Diverse cell-surface molecules are thought to be key for defining neuronal identity, and they mediate interneuronal interactions for structural and functional organization2–6. However, the precise mechanisms that control the fine neuronal organization of the neocortex remain largely unclear. Here, by integrating in-depth single-cell RNA-sequencing analysis, progenitor lineage labelling and mosaic functional analysis, we report that the diverse yet patterned expression of clustered protocadherins (cPCDHs)—the largest subgroup of the cadherin superfamily of cell-adhesion molecules7—regulates the precise spatial arrangement and synaptic connectivity of excitatory neurons in the mouse neocortex. The expression of cPcdh genes in individual neocortical excitatory neurons is diverse yet exhibits distinct composition patterns linked to their developmental origin and spatial positioning. A reduction in functional cPCDH expression causes a lateral clustering of clonally related excitatory neurons originating from the same neural progenitor and a significant increase in synaptic connectivity. By contrast, overexpression of a single cPCDH isoform leads to a lateral dispersion of clonally related excitatory neurons and a considerable decrease in synaptic connectivity. These results suggest that patterned cPCDH expression biases fine spatial and functional organization of individual neocortical excitatory neurons in the mammalian brain. © 2022, The Author(s), under exclusive licence to Springer Nature Limited. |
| Keywords: | controlled study; protein expression; unclassified drug; nonhuman; genetic analysis; protein function; animal cell; mouse; animal; metabolism; animals; mice; animal tissue; gene overexpression; gene expression; embryo; animal experiment; protein; neural stem cell; neurons; cell lineage; brain; brain development; interneuron; mammal; interneurons; neocortex; mammals; cadherin; cadherins; nerve cell; brain function; cell labeling; spatial analysis; nerve cell stimulation; cell component; male; female; article; connectome; single cell rna seq; clustered protocadherin derivative; protocadherin; protocadherins |
| Journal Title: | Nature |
| Volume: | 612 |
| Issue: | 7940 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2022-12-15 |
| Start Page: | 503 |
| End Page: | 511 |
| Language: | English |
| DOI: | 10.1038/s41586-022-05495-2 |
| PUBMED: | 36477535 |
| PROVIDER: | scopus |
| PMCID: | PMC10249668 |
| DOI/URL: | |
| Notes: | Article -- MSK author Xiaohui Lyu's last name is misspelled on the original publication -- Export Date: 3 January 2023 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work