Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication
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 migratio...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
4 December 2019
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| In: |
Science advances
Year: 2019, Volume: 5, Issue: 12 |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.aaw7908 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1126/sciadv.aaw7908 Verlag: https://advances.sciencemag.org/content/5/12/eaaw7908 
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Gesehen am 24.01.2020 |
| Physical Description: | Online Resource |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.aaw7908 |