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

• 成果类型: Article
• 署名作者: Kiefer, Lea; Chiosso, Anna; Langen, Jennifer; Buckley, Alex; Gaudin, Simon; Rajkumar, Sandy M.; Servito, Gabrielle Isabelle F.; Cha, Elizabeth S.; Vijay, Akshara; Yeung, Albert; Horta, Adan; Mui, Michael H.; Canzio, Daniele
• 署名单位: University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Ecole Normale Superieure de Lyon (ENS de LYON); University of California System; University of California Berkeley; Chan Zuckerberg Initiative (CZI)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13314
• DOI: 10.1126/science.adf8440
• 发表日期: 2023-06-01
• 页码: 1236-+
• 关键词: surface recognition code; gene-expression; self-avoidance; alpha family; cohesin; ctcf; ORGANIZATION; promoter; genome; generation

摘要

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.