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

• DOI: 10.1126/science.adf8440
• Publication Date: 2023-06-22T20:14:26Z
• Authors: Lea Kiefer; Anna Chiosso; Jennifer Langen; Alex Buckley; Simon Gaudin; Sandy M. Rajkumar; Gabrielle Isabell...; Elizabeth S. Cha; Akshara Vijay; Albert Yeung; Adan Horta; Michael H. Mui; Daniele Canzio
• Keywords: Protocadherin; Forebrain

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