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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)eaaw7908
JournalScience Advances
Volume5
Issue number12
DOIs
Publication statusPublished - Dec 1 2019

ASJC Scopus subject areas

  • Physics and Astronomy (miscellaneous)
  • General

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