RT Journal Article SR Electronic T1 7q11.23 Syndromes Reveal BAZ1B as a Master Regulator of the Modern Human Face and Validate the Self-Domestication Hypothesis JF bioRxiv FD Cold Spring Harbor Laboratory SP 570036 DO 10.1101/570036 A1 Matteo Zanella A1 Alessandro Vitriolo A1 Alejandro Andirko A1 Pedro Tiago Martins A1 Stefanie Sturm A1 Thomas O’Rourke A1 Magdalena Laugsch A1 Natascia Malerba A1 Adrianos Skaros A1 Sebastiano Trattaro A1 Pierre-Luc Germain A1 Giuseppe Merla A1 Alvaro Rada-Iglesias A1 Cedric Boeckx A1 Giuseppe Testa YR 2019 UL http://biorxiv.org/content/early/2019/03/06/570036.abstract AB 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.