Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication

• Verfasst von: Zanella, Matteo [VerfasserIn]
• Verfasst von: Laugsch, Magdalena [VerfasserIn]
• Titel: Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication
• Verf.angabe: Matteo Zanella, Alessandro Vitriolo, Alejandro Andirko, Pedro Tiago Martins, Stefanie Sturm, Thomas O’Rourke, Magdalena Laugsch, Natascia Malerba, Adrianos Skaros, Sebastiano Trattaro, Pierre-Luc Germain, Marija Mihailovic, Giuseppe Merla, Alvaro Rada-Iglesias, Cedric Boeckx, Giuseppe Testa
• E-Jahr: 2019
• Jahr: 4 December 2019
• Umfang: 16 S.
• Fussnoten: Gesehen am 24.01.2020
• Titel Quelle: Enthalten in: Science advances
• Ort Quelle: Washington, DC [u.a.] : Assoc., 2015
• Jahr Quelle: 2019
• Band/Heft Quelle: 5(2019,12) Artikel-Nummer eaaw7908, 16 Seiten
• ISSN Quelle: 2375-2548
• DOI: doi:10.1126/sciadv.aaw7908
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1688497986

Abstract

We undertook a functional dissection of chromatin remodeler BAZ1B in neural crest (NC) stem cells (NCSCs) from a uniquely informative cohort of typical and atypical patients harboring 7q11.23 copy number variants. Our results reveal a key contribution of BAZ1B to NCSC in vitro induction and migration, coupled with a crucial involvement in NC-specific transcriptional circuits and distal regulation. By intersecting our experimental data with new paleogenetic analyses comparing modern and archaic humans, we found a modern-specific enrichment for regulatory changes both in BAZ1B and its experimentally defined downstream targets, thereby providing the first empirical validation of the human self-domestication hypothesis and positioning BAZ1B as a master regulator of the modern human face. In so doing, we provide experimental evidence that the craniofacial and cognitive/behavioral phenotypes caused by alterations of the Williams-Beuren syndrome critical region can serve as a powerful entry point into the evolution of the modern human face and prosociality. - Dissecting the BAZ1B genetic circuitry in the neural crest brings out its critical role in shaping the modern human face. - Dissecting the BAZ1B genetic circuitry in the neural crest brings out its critical role in shaping the modern human face.