TY - JOUR T1 - 7q11.23 Syndromes Reveal BAZ1B as a Master Regulator of the Modern Human Face and Validate the Self-Domestication Hypothesis JF - bioRxiv DO - 10.1101/570036 SP - 570036 AU - Matteo Zanella AU - Alessandro Vitriolo AU - Alejandro Andirko AU - Pedro Tiago Martins AU - Stefanie Sturm AU - Thomas O’Rourke AU - Magdalena Laugsch AU - Natascia Malerba AU - Adrianos Skaros AU - Sebastiano Trattaro AU - Pierre-Luc Germain AU - Giuseppe Merla AU - Alvaro Rada-Iglesias AU - Cedric Boeckx AU - Giuseppe Testa Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/03/06/570036.abstract N2 - Symmetrical 7q11.23 dosage alterations cause craniofacial and cognitive/behavioral phenotypes that provide a privileged entry point into the evolution of the modern human face and (pro-) sociality. We undertook a functional dissection of chromatin remodeler BAZ1B in neural crest stem cells (NCSCs) from a uniquely informative cohort of typical and atypical patients harboring 7q11.23 Copy Number Variants (CNVs). Our results reveal a key contribution of BAZ1B to NCSC in vitro induction and migration, coupled with a crucial involvement in neural crest (NC)-specific transcriptional circuits and distal regulation. By intersecting our experimental data with new paleogenetic analyses comparing modern and archaic humans, we uncover a modern-specific enrichment for regulatory changes both in BAZ1B and its experimentally defined downstream targets, thereby providing the first empirical validation of the self-domestication hypothesis and positioning BAZ1B as a master regulator of the modern human face.One Sentence Summary BAZ1B dosage shapes the modern human face. ER -