WAPL functions as a rheostat of Protocadherin isoform diversity that controls neural wiring

Kiefer, Lea; Chiosso, Anna; Jennifer, Langen,; Buckley, Alex; Rajkumar, Sandy M.; Servito, Gabrielle Isabelle; Gaudin, Simon; Cha, Elizabeth; Vijay, Akshara; Yeung, Albert; Horta, Adan; Mui, Michael; Canzio, Daniele

doi:10.5281/zenodo.7613545

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“…Source data have been deposited in NCBI’s Gene Expression Omnibus and are accessible through GEO series accession number GSE191195. Custom scripts can be found at Zenodo ( 67 ).…”

Section: Acknowledgmentsmentioning

confidence: 99%

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WAPL functions as a rheostat of Protocadherin isoform diversity that controls neural wiring

Kiefer

Chiosso

Langen

et al. 2023

Science

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Neural type–specific expression of clustered Protocadherin (Pcdh) proteins is essential for the establishment of connectivity patterns during brain development. In mammals, deterministic expression of the same Pcdh isoform promotes minimal overlap of tiled projections of serotonergic neuron axons throughout the brain, while stochastic expression of Pcdh genes allows for convergence of tightly packed, overlapping olfactory sensory neuron axons into targeted structures. How can the same gene locus generate opposite transcriptional programs that orchestrate distinct spatial arrangements of axonal patterns? Here, we reveal that cell type–specific Pcdh expression and axonal behavior depend on the activity of cohesin and its unloader, WAPL (wings apart–like protein homolog). While cohesin erases genomic-distance biases in Pcdh choice, WAPL functions as a rheostat of cohesin processivity that determines Pcdh isoform diversity.

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“…Source data have been deposited in NCBI’s Gene Expression Omnibus and are accessible through GEO series accession number GSE191195. Custom scripts can be found at Zenodo ( 67 ).…”

Section: Acknowledgmentsmentioning

confidence: 99%

“…Source data have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO series accession number GSE191195. Custom scripts can be found at Zenodo (67). License information: Copyright © 2023 the authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.…”

Section: Acknowledgmentsmentioning

confidence: 99%